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(A) Hemodialysis, postprocedure (A) Continue lisinopril; add furosemide (B) Intravenous isotonic bicarbonate, pre- and (B) Continue lisinopril; recheck laboratory studies in postprocedure 2 weeks (C) Intravenous 0.9% saline, pre- and postprocedure (C) Discontinue lisinopril; add furosemide (D) Oral N-acetylcysteine, preprocedure (D) Discontinue lisinopril; add losartan 95

rn @ oe oral Item 5 On physical examination, vital signs are normal. There p= is symmetric 2+ pitting edema of the lower extremities. The wn A 32-year-old man is evaluated for end-stage kidney disease 7) remainder of the examination is unremarkable. @ due to congenital reflux nephropathy. He began hemodialy- wn 7%) sis at age 21 years. He is on the kidney transplant list. He also Laboratory studies: = has hypertension. Medications are amlodipine, calcitriol, Albumin 2.1 g/dL (21 g/L) @o —] vr lisinopril, and sevelamer carbonate. Total cholesterol 359 mg/dL (9.3 mmol/L) Creatinine 0.8 mg/dL (70.7 umol/L) o On physical examination, vital signs are normal. There 7) (onal is a left upper extremity arteriovenous fistula with strong Urine protein-creatinine ratio 5500 mg/g thrill. The remainder of the examination is normal. Kidney ultrasound shows small kidneys with multiple Which of the following is the most likely complication to cysts bilaterally. A few cysts have internal septations. There develop in this patient during the next 12 months? are no solid components or evidence of vascular flow within (A) Diabetes mellitus the cysts. (B) End-stage kidney disease (C) Pulmonary hemorrhage Which of the following is the most appropriate (D) Venous thromboembolism management of this patient’s acquired kidney cysts?

are no solid components or evidence of vascular flow within (A) Diabetes mellitus the cysts. (B) End-stage kidney disease (C) Pulmonary hemorrhage Which of the following is the most appropriate (D) Venous thromboembolism management of this patient’s acquired kidney cysts? (A) Annual kidney ultrasonography (B) Bilateral nephrectomy Item 8 (C) Tolvaptan therapy A 53-year-old woman is evaluated for an increase in her (D) No intervention serum creatinine level. History is significant for long-standing hypertension treated with lisinopril. She reports no changes to her medication regimen during the past year. On physical examination, blood pressure is 145/92 mm ltem 6 Hg, and pulse rate is 84/min; other vital signs are normal. A 69-year-old woman is evaluated for a 2-month history The remainder of the examination is unremarkable. of worsening fatigue, weight loss, and anorexia. She has no Laboratory studies: other medical problems and takes no medications. Creatinine 1.2 mg/dL (106.1 pmol/L); On physical examination, the patient is afebrile. Blood 6 months ago: 0.7 mg/dL pressure is 160/95 mm Hg, pulse rate is 88/min, respiration (61.9 umol/L) rate is 16/min, and oxygen saturation is 100% breathing Estimated glomerular = >52 mL/min/1.73 m? ambient air. The remainder of the examination is unre- filtration rate markable. Urinalysis Specific gravity 1.014; Laboratory studies: pH 5.7; no blood; trace protein Hematocrit 25.5% Urine albumin- 290 mg/g Albumin 3.7 g/dL (37 g/L) creatinine ratio Calcium 10.9 mg/dL (2.7 mmol/L) Creatinine 4.2 mg/dL (371.3 umol/L) Ultrasound reveals normal-sized kidneys with increased Free « light chains Elevated echogenicity; no hydronephrosis or abnormalities of the col- Free A light chains Elevated lecting system are seen. /A Free light chain ratio 4.1 (normal, 0.26-1.65) Urinalysis No blood; 1+ protein Which of the following is the most appropriate management? Urine protein-creatinine ratio 2500 mg/g (A) Obtain kidney biopsy Urine output 2.3 L/24h (B) Obtain random urine protein-creatinine ratio Kidney biopsy confirms the presence of myeloma cast (C) Recheck serum creatinine in 3 months nephropathy. (D) Substitute hydrochlorothiazide for lisinopril

(A) Annual kidney ultrasonography (B) Bilateral nephrectomy Item 8 (C) Tolvaptan therapy A 53-year-old woman is evaluated for an increase in her (D) No intervention serum creatinine level. History is significant for long-standing hypertension treated with lisinopril. She reports no changes to her medication regimen during the past year. On physical examination, blood pressure is 145/92 mm ltem 6 Hg, and pulse rate is 84/min; other vital signs are normal. A 69-year-old woman is evaluated for a 2-month history The remainder of the examination is unremarkable. of worsening fatigue, weight loss, and anorexia. She has no Laboratory studies: other medical problems and takes no medications. Creatinine 1.2 mg/dL (106.1 pmol/L); On physical examination, the patient is afebrile. Blood 6 months ago: 0.7 mg/dL pressure is 160/95 mm Hg, pulse rate is 88/min, respiration (61.9 umol/L) rate is 16/min, and oxygen saturation is 100% breathing Estimated glomerular = >52 mL/min/1.73 m? ambient air. The remainder of the examination is unre- filtration rate markable. Urinalysis Specific gravity 1.014; Laboratory studies: pH 5.7; no blood; trace protein Hematocrit 25.5% Urine albumin- 290 mg/g Albumin 3.7 g/dL (37 g/L) creatinine ratio Calcium 10.9 mg/dL (2.7 mmol/L) Creatinine 4.2 mg/dL (371.3 umol/L) Ultrasound reveals normal-sized kidneys with increased Free « light chains Elevated echogenicity; no hydronephrosis or abnormalities of the col- Free A light chains Elevated lecting system are seen. /A Free light chain ratio 4.1 (normal, 0.26-1.65) Urinalysis No blood; 1+ protein Which of the following is the most appropriate management? Urine protein-creatinine ratio 2500 mg/g (A) Obtain kidney biopsy Urine output 2.3 L/24h (B) Obtain random urine protein-creatinine ratio Kidney biopsy confirms the presence of myeloma cast (C) Recheck serum creatinine in 3 months nephropathy. (D) Substitute hydrochlorothiazide for lisinopril Which of the following is the most appropriate management? Item 9 (A) Chemotherapy A 24-year-old woman is evaluated in the hospital 24 hours (B) Hemodialysis after being admitted for severe preeclampsia. On admission, antihypertensive therapy and intravenous magnesium sul- (C) Hospice referral fate were initiated followed by cesarean section. She con- (D) Plasmapheresis tinues to receive hydralazine, nifedipine, and intravenous magnesium sulfate. On physical examination, temperature is 37.1 °C (98.8 °F), Item 7 blood pressure is 142/90 mm Hg, and pulse rate is 84/min. A 52-year-old man is evaluated during a follow-up visit Abdominal examination reveals a clean, sutured cesarean for membranous nephropathy diagnosed by kidney biopsy section incision without bleeding. There is no oozing from 1 month ago. His medical history is otherwise unremarkable. venipuncture sites. There is 1+ lower extremity edema. The Medications are lisinopril, furosemide, and atorvastatin. remainder of the examination is unremarkable.

Which of the following is the most appropriate management? Item 9 (A) Chemotherapy A 24-year-old woman is evaluated in the hospital 24 hours (B) Hemodialysis after being admitted for severe preeclampsia. On admission, antihypertensive therapy and intravenous magnesium sul- (C) Hospice referral fate were initiated followed by cesarean section. She con- (D) Plasmapheresis tinues to receive hydralazine, nifedipine, and intravenous magnesium sulfate. On physical examination, temperature is 37.1 °C (98.8 °F), Item 7 blood pressure is 142/90 mm Hg, and pulse rate is 84/min. A 52-year-old man is evaluated during a follow-up visit Abdominal examination reveals a clean, sutured cesarean for membranous nephropathy diagnosed by kidney biopsy section incision without bleeding. There is no oozing from 1 month ago. His medical history is otherwise unremarkable. venipuncture sites. There is 1+ lower extremity edema. The Medications are lisinopril, furosemide, and atorvastatin. remainder of the examination is unremarkable. 96

Self-Assessment Test ol Current laboratory studies: od Item 12 a Hemoglobin 7.5 g/dL (75 g/L) ioll A 45-year-old woman is evaluated in the emergency = CONT. Platelet count 84,000/pL (84 x 10°/L) department for a 3-day history of lower extremity weak- re)

A 45-year-old woman is evaluated in the emergency = CONT. Platelet count 84,000/pL (84 x 10°/L) department for a 3-day history of lower extremity weak- re) Alanine aminotransferase 383 U/L S ness. Medical history is significant for hypertension, type wn wn Aspartate aminotransferase 187 U/L wv 2 diabetes mellitus, and gastroesophageal reflux disease. ~n Creatinine 1.3 mg/dL (114.9 umol/L) wn Medications are lisinopril, metformin, canagliflozin, and = A peripheral blood smear shows schistocytes. pantoprazole. = @ On physical examination, vital signs are normal. Knee rn

Alanine aminotransferase 383 U/L S ness. Medical history is significant for hypertension, type wn wn Aspartate aminotransferase 187 U/L wv 2 diabetes mellitus, and gastroesophageal reflux disease. ~n Creatinine 1.3 mg/dL (114.9 umol/L) wn Medications are lisinopril, metformin, canagliflozin, and = A peripheral blood smear shows schistocytes. pantoprazole. = @ On physical examination, vital signs are normal. Knee rn Which of the following is the most appropriate and ankle reflexes are decreased. Muscle strength is 4/5 in treatment? the lower extremities. The remainder of the examination is unremarkable. (A) Continue current therapy Laboratory studies: (B) Start intravenous dexamethasone Creatinine 1.1 mg/dL (97.2 umol/L) (C) Start intravenous eculizumab Electrolytes: (D) Transfuse fresh frozen plasma Sodium 138 mEq/L (138 mmol/L)

Which of the following is the most appropriate and ankle reflexes are decreased. Muscle strength is 4/5 in treatment? the lower extremities. The remainder of the examination is unremarkable. (A) Continue current therapy Laboratory studies: (B) Start intravenous dexamethasone Creatinine 1.1 mg/dL (97.2 umol/L) (C) Start intravenous eculizumab Electrolytes: (D) Transfuse fresh frozen plasma Sodium 138 mEq/L (138 mmol/L) (E) Transfuse packed red blood cells and platelets Potassium 3.0 mEq/L (3.0 mmol/L) Chloride 104 mEq/L (104 mmol/L) Bicarbonate 23 mEq/L (23 mmol/L) Magnesium 1.1 mg/dL (0.45 mmol/L) Item 10 A 63-year-old man is evaluated during a follow-up visit Which of the follow is the most likely cause of this for gastroesophageal reflux disease and heartburn. His patient’s hypokalemia? symptoms are worse after large meals and when lying (A) Canagliflozin down and have significantly decreased the quality of his life and disrupted his sleep. He also has stage G4 chronic (B) Lisinopril kidney disease, obesity, and hypertension. Medications are (C) Pantoprazole atenolol, lisinopril, and nifedipine. (D) Surreptitious diuretic use On physical examination, vital signs are normal. BMI is 38. The remainder of the examination is normal. Laboratory studies show an estimated glomerular fil- Item 13 tration rate of 29 mL/min/1.73 m?. A 32-year-old woman is referred by the public health Weight loss and other lifestyle management mod- department for elevated blood pressure measurements ifications for gastroesophageal reflux disease are dis- during pregnancy. She is at 24 weeks’ gestation of her first cussed. pregnancy. Records document blood pressure measure- ments averaging 140/90 mm Hg before pregnancy. She did Which of the following is the most appropriate additional not have routine medical care before her pregnancy. Her therapy? only medication is a prenatal vitamin. (A) Famotidine On physical examination, blood pressure is 154/ 92 mm Hg; other vital signs are normal. The patient has a (B) Omeprazole gravid uterus consistent with her stage of pregnancy. There (C) Oral calcium carbonate and magnesium hydroxide is trace ankle edema bilaterally. Funduscopic, cardiac, and (D) Sucralfate neurologic examinations are normal. Laboratory studies are normal; urinalysis shows no proteinuria. Item 11 ECG is normal.

(E) Transfuse packed red blood cells and platelets Potassium 3.0 mEq/L (3.0 mmol/L) Chloride 104 mEq/L (104 mmol/L) Bicarbonate 23 mEq/L (23 mmol/L) Magnesium 1.1 mg/dL (0.45 mmol/L) Item 10 A 63-year-old man is evaluated during a follow-up visit Which of the follow is the most likely cause of this for gastroesophageal reflux disease and heartburn. His patient’s hypokalemia? symptoms are worse after large meals and when lying (A) Canagliflozin down and have significantly decreased the quality of his life and disrupted his sleep. He also has stage G4 chronic (B) Lisinopril kidney disease, obesity, and hypertension. Medications are (C) Pantoprazole atenolol, lisinopril, and nifedipine. (D) Surreptitious diuretic use On physical examination, vital signs are normal. BMI is 38. The remainder of the examination is normal. Laboratory studies show an estimated glomerular fil- Item 13 tration rate of 29 mL/min/1.73 m?. A 32-year-old woman is referred by the public health Weight loss and other lifestyle management mod- department for elevated blood pressure measurements ifications for gastroesophageal reflux disease are dis- during pregnancy. She is at 24 weeks’ gestation of her first cussed. pregnancy. Records document blood pressure measure- ments averaging 140/90 mm Hg before pregnancy. She did Which of the following is the most appropriate additional not have routine medical care before her pregnancy. Her therapy? only medication is a prenatal vitamin. (A) Famotidine On physical examination, blood pressure is 154/ 92 mm Hg; other vital signs are normal. The patient has a (B) Omeprazole gravid uterus consistent with her stage of pregnancy. There (C) Oral calcium carbonate and magnesium hydroxide is trace ankle edema bilaterally. Funduscopic, cardiac, and (D) Sucralfate neurologic examinations are normal. Laboratory studies are normal; urinalysis shows no proteinuria. Item 11 ECG is normal. A 38-year-old woman is evaluated in the emergency department for a 4-hour history of left flank pain that Which of the following is the most appropriate radiates to the groin. She is otherwise well and takes no management for this patient’s hypertension? medications. (A) Early delivery of the fetus A noncontrast helical CT scan of the abdomen shows a 11-mm stone in the proximal ureter. There is dilation of the (B) Start hydrochlorothiazide

A 38-year-old woman is evaluated in the emergency department for a 4-hour history of left flank pain that Which of the following is the most appropriate radiates to the groin. She is otherwise well and takes no management for this patient’s hypertension? medications. (A) Early delivery of the fetus A noncontrast helical CT scan of the abdomen shows a 11-mm stone in the proximal ureter. There is dilation of the (B) Start hydrochlorothiazide renal calyces. (C) Start labetalol Analgesics are initiated. (D) Clinical monitoring Which of the following is the most appropriate additional treatment? Item 14 A 34-year-old woman is evaluated for hypertension. During (A co Intravenous 0.9% saline the past 3 months, two blood pressure measurements in (B Lithotripsy health care settings averaged 150/90 mm Hg. During the same (C r—~wao Tamsulosin time period, three blood pressure measurements obtained (D a= Observation outside of health care settings averaged 128/78 mm Hg. 97

Self-Assessment Test 72) @o =a She has no other pertinent personal or family history. She Current laboratory studies: > wn takes no medications. Creatinine 3.4 mg/dL (300.6 umol/L) m1) Oo On physical examination, blood pressure is 144/92 mm Electrolytes: wn wn Hg in both arms, pulse rate is 80/min, and respiration rate Sodium 134 mEq/L (134 mmol/L) =| is 18/min. BMI is 22. The remainder of the examination is Potassium 6.4 mEq/L (6.4 mmol/L) @ s normal. Chloride 100 mEq/L (100 mmol/L) - Bicarbonate 12 mEq/L (12 mmol/L) o mn Which of the following is the most appropriate - Chest radiograph shows diffuse bilateral infiltrates and management? vascular cephalization. (A) Begin chlorthalidone (B) Obtain renal artery imaging Which of the following is the most appropriate therapy? (C) Perform ambulatory blood pressure monitoring (A) Begin continuous renal replacement therapy (D) Recheck blood pressure in the office in 3 months (B) Begin peritoneal dialysis (C) Continue current management (D) Switch to intravenous bumetanide Item 15 A 68-year-old man is evaluated in the emergency depart- ment for generalized weakness that began 12 hours ago after Item 17 ingesting a bottle of magnesium citrate for constipation. He has hypertension, hyperlipidemia, and stage G4 chronic A 23-year-old woman is evaluated for a 1-week history of kidney disease. Medications are furosemide, nifedipine, and muscle weakness. Medical history is significant for chronic simvastatin. migraine headaches. Medications are topiramate, sumatrip- On physical examination, blood pressure is 102/64 mm tan, naproxen, and aspirin. Hg, and pulse rate is 50/min; other vital signs are nor- On physical examination, vital signs are normal. mal. Muscle strength is 4/5 diffusely. Reflexes are absent BMI is 19. The remainder of the examination is unremark- throughout. The remainder of the examination is normal. able.

72) @o =a She has no other pertinent personal or family history. She Current laboratory studies: > wn takes no medications. Creatinine 3.4 mg/dL (300.6 umol/L) m1) Oo On physical examination, blood pressure is 144/92 mm Electrolytes: wn wn Hg in both arms, pulse rate is 80/min, and respiration rate Sodium 134 mEq/L (134 mmol/L) =| is 18/min. BMI is 22. The remainder of the examination is Potassium 6.4 mEq/L (6.4 mmol/L) @ s normal. Chloride 100 mEq/L (100 mmol/L) - Bicarbonate 12 mEq/L (12 mmol/L) o mn Which of the following is the most appropriate - Chest radiograph shows diffuse bilateral infiltrates and management? vascular cephalization. (A) Begin chlorthalidone (B) Obtain renal artery imaging Which of the following is the most appropriate therapy? (C) Perform ambulatory blood pressure monitoring (A) Begin continuous renal replacement therapy (D) Recheck blood pressure in the office in 3 months (B) Begin peritoneal dialysis (C) Continue current management (D) Switch to intravenous bumetanide Item 15 A 68-year-old man is evaluated in the emergency depart- ment for generalized weakness that began 12 hours ago after Item 17 ingesting a bottle of magnesium citrate for constipation. He has hypertension, hyperlipidemia, and stage G4 chronic A 23-year-old woman is evaluated for a 1-week history of kidney disease. Medications are furosemide, nifedipine, and muscle weakness. Medical history is significant for chronic simvastatin. migraine headaches. Medications are topiramate, sumatrip- On physical examination, blood pressure is 102/64 mm tan, naproxen, and aspirin. Hg, and pulse rate is 50/min; other vital signs are nor- On physical examination, vital signs are normal. mal. Muscle strength is 4/5 diffusely. Reflexes are absent BMI is 19. The remainder of the examination is unremark- throughout. The remainder of the examination is normal. able. Laboratory studies: Laboratory studies: Calcium 8.4 mg/dL (2.1 mmol/L) Electrolytes: Creatinine 5.5 mg/dL (486.2 umol/L) Sodium 142 mEq/L (142 mmol/L) Magnesium 6.8 mg/dL (2.8 mmol/L) Potassium 3.1 mEq/L (3.1 mmol/L) Phosphorus 5.5 mg/dL (1.8 mmol/L) Chloride 120 mEq/L (120 mmol/L) Bicarbonate 15 mEq/L (15 mmol/L) Which of the following is the most appropriate immediate Urine sodium 18 mEq/L (18 mmol/L) treatment? Urine potassium 8.0 mEq/L (8.0 mmol/L) Urine chloride 32 mEq/L (32 mmol/L) (A) Intravenous calcium gluconate (B) Intravenous furosemide Which of the following is the most likely cause of this (C) Intravenous sodium bicarbonate patient’s metabolic acidosis? (D) Oral patiromer (A) Salicylate toxicity (B) Surreptitious furosemide use (C) Surreptitious laxative use ltem 16 (D) Topiramate A 77-year-old woman is evaluated in the ICU for acute kidney injury after being hospitalized 2 days ago for septic shock and acute respiratory distress syndrome secondary to community-acquired pneumonia. She was intubated and Item 18 vasopressor support was initiated. Over the first 18 hours A 57-year-old man is evaluated during a follow-up visit of hospitalization, she received 3600 mL of Ringer’s lactate for stable chronic kidney disease diagnosed 1 year ago. solution. Current medications are norepinephrine, ceftaro- Renal duplex Doppler ultrasound at that time showed line, levofloxacin, and dexmedetomidine. a 7-cm right kidney and 11-cm left kidney with a >75% On physical examination, the patient is mechanically midstenotic lesion of the left renal artery. He also has type ventilated. Temperature is 38.4 °C (101.1 °F), blood pres- 2 diabetes mellitus, hyperlipidemia, and peripheral artery sure is 88/52 mm Hg, pulse rate is 105/min, respiration disease. Medications are low-dose aspirin, furosemide, lis- rate is 16/min, and oxygen saturation is 90% with the inopril, amlodipine, carvedilol, metformin, empagliflozin, patient breathing 50% Fio,. Diffusely coarse breath sounds and atorvastatin. are heard on pulmonary examination. A central venous On physical examination, blood pressure is 128/74 mm catheter is in place; central venous pressure measurement Hg, pulse rate is 65/min, and respiration rate is 18/min. is 14mm Hg. Bilateral carotid and lower abdominal quadrant bruits are Urine output is 30 mL/h and unresponsive to escalating heard. Peripheral extremity pulses are diminished. The doses of intravenous furosemide. remainder of the examination is normal.

Laboratory studies: Laboratory studies: Calcium 8.4 mg/dL (2.1 mmol/L) Electrolytes: Creatinine 5.5 mg/dL (486.2 umol/L) Sodium 142 mEq/L (142 mmol/L) Magnesium 6.8 mg/dL (2.8 mmol/L) Potassium 3.1 mEq/L (3.1 mmol/L) Phosphorus 5.5 mg/dL (1.8 mmol/L) Chloride 120 mEq/L (120 mmol/L) Bicarbonate 15 mEq/L (15 mmol/L) Which of the following is the most appropriate immediate Urine sodium 18 mEq/L (18 mmol/L) treatment? Urine potassium 8.0 mEq/L (8.0 mmol/L) Urine chloride 32 mEq/L (32 mmol/L) (A) Intravenous calcium gluconate (B) Intravenous furosemide Which of the following is the most likely cause of this (C) Intravenous sodium bicarbonate patient’s metabolic acidosis? (D) Oral patiromer (A) Salicylate toxicity (B) Surreptitious furosemide use (C) Surreptitious laxative use ltem 16 (D) Topiramate A 77-year-old woman is evaluated in the ICU for acute kidney injury after being hospitalized 2 days ago for septic shock and acute respiratory distress syndrome secondary to community-acquired pneumonia. She was intubated and Item 18 vasopressor support was initiated. Over the first 18 hours A 57-year-old man is evaluated during a follow-up visit of hospitalization, she received 3600 mL of Ringer’s lactate for stable chronic kidney disease diagnosed 1 year ago. solution. Current medications are norepinephrine, ceftaro- Renal duplex Doppler ultrasound at that time showed line, levofloxacin, and dexmedetomidine. a 7-cm right kidney and 11-cm left kidney with a >75% On physical examination, the patient is mechanically midstenotic lesion of the left renal artery. He also has type ventilated. Temperature is 38.4 °C (101.1 °F), blood pres- 2 diabetes mellitus, hyperlipidemia, and peripheral artery sure is 88/52 mm Hg, pulse rate is 105/min, respiration disease. Medications are low-dose aspirin, furosemide, lis- rate is 16/min, and oxygen saturation is 90% with the inopril, amlodipine, carvedilol, metformin, empagliflozin, patient breathing 50% Fio,. Diffusely coarse breath sounds and atorvastatin. are heard on pulmonary examination. A central venous On physical examination, blood pressure is 128/74 mm catheter is in place; central venous pressure measurement Hg, pulse rate is 65/min, and respiration rate is 18/min. is 14mm Hg. Bilateral carotid and lower abdominal quadrant bruits are Urine output is 30 mL/h and unresponsive to escalating heard. Peripheral extremity pulses are diminished. The doses of intravenous furosemide. remainder of the examination is normal. 98

7 Self-Assessment Test het Laboratory studies: Which of the following is the most likely cause of this ct _— Creatinine 1.4 mg/dL (123.8 umol/L) spect patient’s hypophosphatemia? = ao Electrolytes Normal (A) Chronic kidney disease £ Estimated glomerular filtration 45 mL/min/1.73 m? wn rate (B) Increased fibroblast growth factor 23 production wn a wn Urine albumin-creatinine ratio 1100 mg/g (C) Intracellular shift of phosphorus wa

rate (B) Increased fibroblast growth factor 23 production wn a wn Urine albumin-creatinine ratio 1100 mg/g (C) Intracellular shift of phosphorus wa (D) Osmotic diuresis tn Which of the following is the most appropriate management? = c-F) (E) Proximal renal tubular dysfunction nr (A) Left renal artery angioplasty (B) Renal artery CT angiography (C) Renal artery MR angiography Item 21 (D) No additional diagnostic testing A 25-year-old woman is evaluated for a 6-month history of fatigue, joint pain, sun sensitivity, and pleuritic chest pain. Item 19 Medications are an oral contraceptive pill and as-needed naproxen. A 46-year-old woman is evaluated for a serum creatinine On physical examination, temperature is 38.2 °C level of 2.6 mg/dL (229.8 umol/L). Her baseline serum cre- (100.8 °F), blood pressure is 142/90 mm Hg, and pulse rate atinine level 3 months ago was 0.9 mg/dL (79.6 umol/L). is 100/min. The fingers and wrist joints are tender, but there She has no symptoms. Two years ago, she started losar- is no synovitis. The remainder of the examination is normal. tan and amlodipine for hypertension. One year ago, she Laboratory studies show a serum creatinine level of started omeprazole for gastroesophageal reflux disease and 1.4mg/dL (123.8 pmol/L); dipstick urinalysis shows 2+ blood, naproxen for knee osteoarthritis. Eight months ago, she 3+ protein, positive leukocyte esterase, and no nitrites. began atorvastatin for hyperlipidemia. Urine microscopy is shown. On physical examination, temperature is 37.0 °C (98.6 °F), and blood pressure is 138/86 mm Hg. The remainder of the examination is unremarkable. Urinalysis shows the following: specific gravity 1.015; PH 5.5; 1+ erythrocytes; 3+ leukocytes; 1+ leukocyte ester- ase; no nitrates; and >100 leukocytes/hpf with leukocyte and granular casts.

(D) Osmotic diuresis tn Which of the following is the most appropriate management? = c-F) (E) Proximal renal tubular dysfunction nr (A) Left renal artery angioplasty (B) Renal artery CT angiography (C) Renal artery MR angiography Item 21 (D) No additional diagnostic testing A 25-year-old woman is evaluated for a 6-month history of fatigue, joint pain, sun sensitivity, and pleuritic chest pain. Item 19 Medications are an oral contraceptive pill and as-needed naproxen. A 46-year-old woman is evaluated for a serum creatinine On physical examination, temperature is 38.2 °C level of 2.6 mg/dL (229.8 umol/L). Her baseline serum cre- (100.8 °F), blood pressure is 142/90 mm Hg, and pulse rate atinine level 3 months ago was 0.9 mg/dL (79.6 umol/L). is 100/min. The fingers and wrist joints are tender, but there She has no symptoms. Two years ago, she started losar- is no synovitis. The remainder of the examination is normal. tan and amlodipine for hypertension. One year ago, she Laboratory studies show a serum creatinine level of started omeprazole for gastroesophageal reflux disease and 1.4mg/dL (123.8 pmol/L); dipstick urinalysis shows 2+ blood, naproxen for knee osteoarthritis. Eight months ago, she 3+ protein, positive leukocyte esterase, and no nitrites. began atorvastatin for hyperlipidemia. Urine microscopy is shown. On physical examination, temperature is 37.0 °C (98.6 °F), and blood pressure is 138/86 mm Hg. The remainder of the examination is unremarkable. Urinalysis shows the following: specific gravity 1.015; PH 5.5; 1+ erythrocytes; 3+ leukocytes; 1+ leukocyte ester- ase; no nitrates; and >100 leukocytes/hpf with leukocyte and granular casts. Which of the following drugs should be discontinued in this patient?

(D) Osmotic diuresis tn Which of the following is the most appropriate management? = c-F) (E) Proximal renal tubular dysfunction nr (A) Left renal artery angioplasty (B) Renal artery CT angiography (C) Renal artery MR angiography Item 21 (D) No additional diagnostic testing A 25-year-old woman is evaluated for a 6-month history of fatigue, joint pain, sun sensitivity, and pleuritic chest pain. Item 19 Medications are an oral contraceptive pill and as-needed naproxen. A 46-year-old woman is evaluated for a serum creatinine On physical examination, temperature is 38.2 °C level of 2.6 mg/dL (229.8 umol/L). Her baseline serum cre- (100.8 °F), blood pressure is 142/90 mm Hg, and pulse rate atinine level 3 months ago was 0.9 mg/dL (79.6 umol/L). is 100/min. The fingers and wrist joints are tender, but there She has no symptoms. Two years ago, she started losar- is no synovitis. The remainder of the examination is normal. tan and amlodipine for hypertension. One year ago, she Laboratory studies show a serum creatinine level of started omeprazole for gastroesophageal reflux disease and 1.4mg/dL (123.8 pmol/L); dipstick urinalysis shows 2+ blood, naproxen for knee osteoarthritis. Eight months ago, she 3+ protein, positive leukocyte esterase, and no nitrites. began atorvastatin for hyperlipidemia. Urine microscopy is shown. On physical examination, temperature is 37.0 °C (98.6 °F), and blood pressure is 138/86 mm Hg. The remainder of the examination is unremarkable. Urinalysis shows the following: specific gravity 1.015; PH 5.5; 1+ erythrocytes; 3+ leukocytes; 1+ leukocyte ester- ase; no nitrates; and >100 leukocytes/hpf with leukocyte and granular casts. Which of the following drugs should be discontinued in this patient? (A) Atorvastatin and amlodipine (B) Losartan and amlodipine (C) Losartan and omeprazole (D) Naproxen and atorvastatin (E) Naproxen and omeprazole

(D) Osmotic diuresis tn Which of the following is the most appropriate management? = c-F) (E) Proximal renal tubular dysfunction nr (A) Left renal artery angioplasty (B) Renal artery CT angiography (C) Renal artery MR angiography Item 21 (D) No additional diagnostic testing A 25-year-old woman is evaluated for a 6-month history of fatigue, joint pain, sun sensitivity, and pleuritic chest pain. Item 19 Medications are an oral contraceptive pill and as-needed naproxen. A 46-year-old woman is evaluated for a serum creatinine On physical examination, temperature is 38.2 °C level of 2.6 mg/dL (229.8 umol/L). Her baseline serum cre- (100.8 °F), blood pressure is 142/90 mm Hg, and pulse rate atinine level 3 months ago was 0.9 mg/dL (79.6 umol/L). is 100/min. The fingers and wrist joints are tender, but there She has no symptoms. Two years ago, she started losar- is no synovitis. The remainder of the examination is normal. tan and amlodipine for hypertension. One year ago, she Laboratory studies show a serum creatinine level of started omeprazole for gastroesophageal reflux disease and 1.4mg/dL (123.8 pmol/L); dipstick urinalysis shows 2+ blood, naproxen for knee osteoarthritis. Eight months ago, she 3+ protein, positive leukocyte esterase, and no nitrites. began atorvastatin for hyperlipidemia. Urine microscopy is shown. On physical examination, temperature is 37.0 °C (98.6 °F), and blood pressure is 138/86 mm Hg. The remainder of the examination is unremarkable. Urinalysis shows the following: specific gravity 1.015; PH 5.5; 1+ erythrocytes; 3+ leukocytes; 1+ leukocyte ester- ase; no nitrates; and >100 leukocytes/hpf with leukocyte and granular casts. Which of the following drugs should be discontinued in this patient? (A) Atorvastatin and amlodipine (B) Losartan and amlodipine (C) Losartan and omeprazole (D) Naproxen and atorvastatin (E) Naproxen and omeprazole Item 20 A 56-year-old man is evaluated for weakness after complet- ing a second cycle of chemotherapy for a soft-tissue sarcoma recently excised from the right thigh. Medications are ifos- famide, doxorubicin, and mesna. On physical examination, vital signs are normal. The patient appears well. Generalized weakness is noted. There is a healing surgical scar on the upper right thigh. The Which of the following is the most appropriate test? remainder of the examination is normal. (A) Cystoscopy Laboratory studies: (B) Kidney biopsy Creatinine 1.6 mg/dL (141.4 umol/L) (C) Kidney ultrasonography Electrolytes: Sodium 136 mEq/L (136 mmol/L) (D) Urine culture Potassium 3.5 mEq/L (3.5 mmol/L) Chloride 106 mEq/L (106 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) Item 22 Glucose 88 mg/dL (4.9 mmol/L) A 42-year-old man is evaluated during a follow-up visit Phosphorus 1.2 mg/dL (0.39 mmol/L) for recently confirmed primary hypertension. Hypertension Fractional excretion of 10% was confirmed with multiple home blood pressure monitor- phosphorus ing readings that averaged 148/98 mm Hg. Chlorthalidone Urinalysis pH 7.0; no blood; 3+ protein; 2+ was initiated 1 month ago, and home blood pressure mon- glucose; no leukocyte esterase itoring showed readings above target despite adherence to

Item 20 A 56-year-old man is evaluated for weakness after complet- ing a second cycle of chemotherapy for a soft-tissue sarcoma recently excised from the right thigh. Medications are ifos- famide, doxorubicin, and mesna. On physical examination, vital signs are normal. The patient appears well. Generalized weakness is noted. There is a healing surgical scar on the upper right thigh. The Which of the following is the most appropriate test? remainder of the examination is normal. (A) Cystoscopy Laboratory studies: (B) Kidney biopsy Creatinine 1.6 mg/dL (141.4 umol/L) (C) Kidney ultrasonography Electrolytes: Sodium 136 mEq/L (136 mmol/L) (D) Urine culture Potassium 3.5 mEq/L (3.5 mmol/L) Chloride 106 mEq/L (106 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) Item 22 Glucose 88 mg/dL (4.9 mmol/L) A 42-year-old man is evaluated during a follow-up visit Phosphorus 1.2 mg/dL (0.39 mmol/L) for recently confirmed primary hypertension. Hypertension Fractional excretion of 10% was confirmed with multiple home blood pressure monitor- phosphorus ing readings that averaged 148/98 mm Hg. Chlorthalidone Urinalysis pH 7.0; no blood; 3+ protein; 2+ was initiated 1 month ago, and home blood pressure mon- glucose; no leukocyte esterase itoring showed readings above target despite adherence to 99

Self-Assessment Test 4) o sa lifestyle interventions and medication. He has no other med- Laboratory studies: > ical problems and takes no other medication. The patient is Creatinine 2.0 mg/dL (176.8 pmol/L) wna wn @ Black. Electrolytes: wn wn On physical examination, blood pressure is 144/94 mm Sodium 140 mEq/L (140 mmol/L) =} Hg, and pulse rate is 72/min; other vital signs are normal. Potassium 5.0 mEq/L (5.0 mmol/L) @ = BMI is 22. The remainder of the examination is normal. Chloride 112 mEq/L (112 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) - Laboratory studies show a serum creatinine level of > 1.0 mg/dL (88.4 umol/L) and a serum potassium level of Urinalysis Specific gravity 1.015; pH wn ona 3.5 mEq/L (3.5 mmol/L). 6.5; no blood; 1+ protein; 1+ leukocytes; 2-5 leukocytes/hpf; Which of the following is the most appropriate additional 0-2 erythrocytes/hpf; no casts treatment? Urine protein-creatinine 400 mg/g ratio (A) Amlodipine Kidney ultrasound shows a 9.9-cm right kidney and a (B) Doxazosin 10.3-cm left kidney with increased cortical echogenicity and (C) Hydralazine mild thinning; there is no hydronephrosis. (D) Metoprolol Which of the following is the most likely diagnosis?

4) o sa lifestyle interventions and medication. He has no other med- Laboratory studies: > ical problems and takes no other medication. The patient is Creatinine 2.0 mg/dL (176.8 pmol/L) wna wn @ Black. Electrolytes: wn wn On physical examination, blood pressure is 144/94 mm Sodium 140 mEq/L (140 mmol/L) =} Hg, and pulse rate is 72/min; other vital signs are normal. Potassium 5.0 mEq/L (5.0 mmol/L) @ = BMI is 22. The remainder of the examination is normal. Chloride 112 mEq/L (112 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) - Laboratory studies show a serum creatinine level of > 1.0 mg/dL (88.4 umol/L) and a serum potassium level of Urinalysis Specific gravity 1.015; pH wn ona 3.5 mEq/L (3.5 mmol/L). 6.5; no blood; 1+ protein; 1+ leukocytes; 2-5 leukocytes/hpf; Which of the following is the most appropriate additional 0-2 erythrocytes/hpf; no casts treatment? Urine protein-creatinine 400 mg/g ratio (A) Amlodipine Kidney ultrasound shows a 9.9-cm right kidney and a (B) Doxazosin 10.3-cm left kidney with increased cortical echogenicity and (C) Hydralazine mild thinning; there is no hydronephrosis. (D) Metoprolol Which of the following is the most likely diagnosis? (A) Acute interstitial nephritis Item 23 (B) Acute tubular necrosis A 73-year-old woman is evaluated during a follow-up visit (C) Chronic interstitial nephritis for stage G4 chronic kidney disease. She reports no uremic symptoms. Medical history is also significant for hyperten- (D) IgA nephropathy sion. Medications are atenolol, chlorthalidone, cholecalcif- (E) Infection-related glomerulonephritis erol, hydralazine, and nifedipine. The physical examination, including vital signs, is Item 25 normal. A 48-year-old woman is evaluated in the ICU for increasing Laboratory studies: serum creatinine and oliguria; she has cirrhosis. She was Calcium 8.7 mg/dL (2.2 mmol/L) hospitalized 24 hours ago and treated for a bleeding esopha- Creatinine 2.0 mg/dL (176.8 umol/L) geal varix. Outpatient medications are furosemide, spirono- Phosphorus 5.4 mg/dL (1.7 mmol/L) lactone, nadolol, and norfloxacin. On admission, her serum Parathyroid hormone 97 pg/mL (97 ng/L) creatinine level was 1.5 mg/dL (132.6 umol/L). 25-hydroxyvitamin D 60 ng/mL (150 nmol/L) On physical examination, blood pressure is 102/63 mm Estimated glomerular 24 mL/min/1.73 m? Hg, and pulse rate is 66/min; other vital signs are nor- filtration rate mal. Ascites and jaundice are present. The remainder of the examination is normal. Which of the following is the most appropriate Urine output is 190 mL over the past 24 hours. management? Current laboratory studies: (A) Calcitriol Albumin 2.3 g/dL (23 g/L) (B) Calcium acetate Creatinine 2.3 mg/dL (203.3 pmol/L) Electrolytes: (C) Cinacalcet Sodium 126 mEq/L (126 mmol/L) (D) Low phosphate diet Potassium 3.9 mEq/L (3.9 mmol/L) (E) Sevelamer Chloride 95 mEq/L (95 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) Urine sodium <10 mEq/L (10 mmol/L) Item 24 Urinalysis Specific gravity 1.030; pH 5.0; trace A 35-year-old man is evaluated during a follow-up visit protein; 2+ bilirubin; bilirubin staining; for an elevated serum creatinine level. The elevated serum no erythrocytes or leukocytes creatinine was discovered during a recent hospitalization Kidney ultrasound shows normal-appearing kidneys for cellulitis of the right lower leg that was treated with without hydronephrosis. intravenous cephazolin followed by oral cephalexin for Diuretics are withheld, and norepinephrine infusion a total of 7 days of antibiotic therapy. He is a migratory is initiated. agricultural worker. He works in the northeastern United States during summer months and returns to Guatemala Which of the following is the most appropriate additional for the remainder of the year performing similar work. treatment? The patient has no other medical problems and takes no (A) Hemodialysis medications. On physical examination, blood pressure is 138/90 mm (B) Intravenous albumin Hg; other vital signs are normal. BMI is 27. The remainder of (C) Oral midodrine and intravenous octreotide the examination is normal. (D) Transjugular intrahepatic portosystemic shunt

(A) Acute interstitial nephritis Item 23 (B) Acute tubular necrosis A 73-year-old woman is evaluated during a follow-up visit (C) Chronic interstitial nephritis for stage G4 chronic kidney disease. She reports no uremic symptoms. Medical history is also significant for hyperten- (D) IgA nephropathy sion. Medications are atenolol, chlorthalidone, cholecalcif- (E) Infection-related glomerulonephritis erol, hydralazine, and nifedipine. The physical examination, including vital signs, is Item 25 normal. A 48-year-old woman is evaluated in the ICU for increasing Laboratory studies: serum creatinine and oliguria; she has cirrhosis. She was Calcium 8.7 mg/dL (2.2 mmol/L) hospitalized 24 hours ago and treated for a bleeding esopha- Creatinine 2.0 mg/dL (176.8 umol/L) geal varix. Outpatient medications are furosemide, spirono- Phosphorus 5.4 mg/dL (1.7 mmol/L) lactone, nadolol, and norfloxacin. On admission, her serum Parathyroid hormone 97 pg/mL (97 ng/L) creatinine level was 1.5 mg/dL (132.6 umol/L). 25-hydroxyvitamin D 60 ng/mL (150 nmol/L) On physical examination, blood pressure is 102/63 mm Estimated glomerular 24 mL/min/1.73 m? Hg, and pulse rate is 66/min; other vital signs are nor- filtration rate mal. Ascites and jaundice are present. The remainder of the examination is normal. Which of the following is the most appropriate Urine output is 190 mL over the past 24 hours. management? Current laboratory studies: (A) Calcitriol Albumin 2.3 g/dL (23 g/L) (B) Calcium acetate Creatinine 2.3 mg/dL (203.3 pmol/L) Electrolytes: (C) Cinacalcet Sodium 126 mEq/L (126 mmol/L) (D) Low phosphate diet Potassium 3.9 mEq/L (3.9 mmol/L) (E) Sevelamer Chloride 95 mEq/L (95 mmol/L) Bicarbonate 18 mEq/L (18 mmol/L) Urine sodium <10 mEq/L (10 mmol/L) Item 24 Urinalysis Specific gravity 1.030; pH 5.0; trace A 35-year-old man is evaluated during a follow-up visit protein; 2+ bilirubin; bilirubin staining; for an elevated serum creatinine level. The elevated serum no erythrocytes or leukocytes creatinine was discovered during a recent hospitalization Kidney ultrasound shows normal-appearing kidneys for cellulitis of the right lower leg that was treated with without hydronephrosis. intravenous cephazolin followed by oral cephalexin for Diuretics are withheld, and norepinephrine infusion a total of 7 days of antibiotic therapy. He is a migratory is initiated. agricultural worker. He works in the northeastern United States during summer months and returns to Guatemala Which of the following is the most appropriate additional for the remainder of the year performing similar work. treatment? The patient has no other medical problems and takes no (A) Hemodialysis medications. On physical examination, blood pressure is 138/90 mm (B) Intravenous albumin Hg; other vital signs are normal. BMI is 27. The remainder of (C) Oral midodrine and intravenous octreotide the examination is normal. (D) Transjugular intrahepatic portosystemic shunt 100

; Self-Assessment Test i Item 26 Item 29 ® — ent A 43-year-old man is evaluated during a routine follow-up A 54-year-old man is evaluated during a new patient visit. He < visit for end-stage kidney disease due to IgA nephropathy. He C.F) has a 30-year history of type 2 diabetes mellitus and 10-year received a living-donor related kidney transplant 5 years ago. £ history of hypertension. Medical history is also significant for wn rn He is asymptomatic. Medical history is also significant for obesity and hypercholesterolemia. Medications are amlodip- <7) hypertension. Medications are prednisone, mycophenolate ine, atorvastatin, canagliflozin, metformin, and lisinopril- a mofetil, tacrolimus, lisinopril, metoprolol, and atorvastatin. hydrochlorothiazide. At his last visit to his previous physician, i — All physical examination findings, including vital signs, serum creatinine level was 1.4 mg/dL (123.8 umol/L), and ) ” are normal. estimated glomerular filtration rate was 58 mL/min/1.73 m2. Laboratory studies show a serum creatinine level of On physical examination, blood pressure is 158/82 mm 0.8 mg/dL (70.7 mol/L) and a fasting blood glucose level of Hg, and pulse rate is 62/min; other vital signs are normal. 99 mg/dL (5.5 mmol/L). BMI is 38. The remainder of the examination is normal.

Item 26 Item 29 ® — ent A 43-year-old man is evaluated during a routine follow-up A 54-year-old man is evaluated during a new patient visit. He < visit for end-stage kidney disease due to IgA nephropathy. He C.F) has a 30-year history of type 2 diabetes mellitus and 10-year received a living-donor related kidney transplant 5 years ago. £ history of hypertension. Medical history is also significant for wn rn He is asymptomatic. Medical history is also significant for obesity and hypercholesterolemia. Medications are amlodip- <7) hypertension. Medications are prednisone, mycophenolate ine, atorvastatin, canagliflozin, metformin, and lisinopril- a mofetil, tacrolimus, lisinopril, metoprolol, and atorvastatin. hydrochlorothiazide. At his last visit to his previous physician, i — All physical examination findings, including vital signs, serum creatinine level was 1.4 mg/dL (123.8 umol/L), and ) ” are normal. estimated glomerular filtration rate was 58 mL/min/1.73 m2. Laboratory studies show a serum creatinine level of On physical examination, blood pressure is 158/82 mm 0.8 mg/dL (70.7 mol/L) and a fasting blood glucose level of Hg, and pulse rate is 62/min; other vital signs are normal. 99 mg/dL (5.5 mmol/L). BMI is 38. The remainder of the examination is normal. Laboratory studies: Which of the following is the most appropriate screening Albumin 3.5 g/dL (35 g/L) test at this time? Creatinine 1.6 mg/dL (141.4 umol/L) (A) Colonoscopy Electrolytes Normal Estimated glomerular filtration 50 mL/min/1.73 m2 (B) Low-dose chest CT rate (C) Oral glucose tolerance test Urinalysis No blood; 2+ protein (D) Skin examination Results of kidney ultrasonography and referral to an ophthalmologist for a dilated retinal examination are pending.

Laboratory studies: Which of the following is the most appropriate screening Albumin 3.5 g/dL (35 g/L) test at this time? Creatinine 1.6 mg/dL (141.4 umol/L) (A) Colonoscopy Electrolytes Normal Estimated glomerular filtration 50 mL/min/1.73 m2 (B) Low-dose chest CT rate (C) Oral glucose tolerance test Urinalysis No blood; 2+ protein (D) Skin examination Results of kidney ultrasonography and referral to an ophthalmologist for a dilated retinal examination are pending. Item 27 A 43-year-old man is evaluated during a follow-up visit for Which of the following is the most appropriate test to a recent biopsy-confirmed diagnosis of IgA nephropathy. assess the prognosis of this patient’s chronic kidney He is asymptomatic. He has no other medical problems and disease? takes no medications. (A) Hemoglobin A,, measurement Physical examination findings, including vital signs, (B ) Kidney biopsy are normal. (C) Serum parathyroid hormone measurement Laboratory studies: Albumin 4.0 g/dL (40 g/L) ( D) Spot urine albumin-creatinine ratio Creatinine 0.95 mg/dL (84 umol/L) Urinalysis 3+ blood; 2+ protein 24-Hour urine protein excretion 725 mg/24h Item 30 A 62-year-old man is evaluated in the emergency depart- Which of the following is the most appropriate management? ment for abrupt onset of sharp chest pain radiating to his

Item 27 A 43-year-old man is evaluated during a follow-up visit for Which of the following is the most appropriate test to a recent biopsy-confirmed diagnosis of IgA nephropathy. assess the prognosis of this patient’s chronic kidney He is asymptomatic. He has no other medical problems and disease? takes no medications. (A) Hemoglobin A,, measurement Physical examination findings, including vital signs, (B ) Kidney biopsy are normal. (C) Serum parathyroid hormone measurement Laboratory studies: Albumin 4.0 g/dL (40 g/L) ( D) Spot urine albumin-creatinine ratio Creatinine 0.95 mg/dL (84 umol/L) Urinalysis 3+ blood; 2+ protein 24-Hour urine protein excretion 725 mg/24h Item 30 A 62-year-old man is evaluated in the emergency depart- Which of the following is the most appropriate management? ment for abrupt onset of sharp chest pain radiating to his (A) upper back that started 90 minutes ago. Medical history Lisinopril includes difficult-to-control hypertension, hyperlipidemia, (B) Mycophenolate mofetil and type 2 diabetes mellitus. Medications are metformin, (C) Omega-3 fatty acids empagliflozin, rosuvastatin, amlodipine, hydrochlorothia- (D) Prednisone zide, and lisinopril. On physical examination, blood pressure is 210/120 mm Hg in the right arm and 180/100 mm Hg in the left arm, Item 28 pulse rate is 118/min, respiration rate is 20/min, and oxygen A 22-year-old woman participating in a marathon is eval- saturation is 97% with the patient breathing ambient air. The uated in the medical tent for headache, confusion, and patient is diaphoretic and in distress. Cardiac examination disorientation after she stopped running at mile 20. This is reveals tachycardia with a 3/6 diastolic murmur heard along her first marathon. the upper left sternal border. Lungs are clear to auscultation. On physical examination, temperature is 38.0 °C The remainder of the examination is unremarkable. (100.4 °F), blood pressure is 110/72 mm Hg, pulse rate is Emergency CT imaging confirms the diagnosis of 110/min, and respiration rate is 20/min. The patient is con- ascending aortic dissection. fused. The remainder of the examination is normal. Referral for emergency surgical consultation is Laboratory studies show a serum sodium level of obtained. 130 mEq/L (130 mmol/L). Which of the following is the most appropriate initial Which of the following is the most appropriate management? intravenous treatment?

(A) upper back that started 90 minutes ago. Medical history Lisinopril includes difficult-to-control hypertension, hyperlipidemia, (B) Mycophenolate mofetil and type 2 diabetes mellitus. Medications are metformin, (C) Omega-3 fatty acids empagliflozin, rosuvastatin, amlodipine, hydrochlorothia- (D) Prednisone zide, and lisinopril. On physical examination, blood pressure is 210/120 mm Hg in the right arm and 180/100 mm Hg in the left arm, Item 28 pulse rate is 118/min, respiration rate is 20/min, and oxygen A 22-year-old woman participating in a marathon is eval- saturation is 97% with the patient breathing ambient air. The uated in the medical tent for headache, confusion, and patient is diaphoretic and in distress. Cardiac examination disorientation after she stopped running at mile 20. This is reveals tachycardia with a 3/6 diastolic murmur heard along her first marathon. the upper left sternal border. Lungs are clear to auscultation. On physical examination, temperature is 38.0 °C The remainder of the examination is unremarkable. (100.4 °F), blood pressure is 110/72 mm Hg, pulse rate is Emergency CT imaging confirms the diagnosis of 110/min, and respiration rate is 20/min. The patient is con- ascending aortic dissection. fused. The remainder of the examination is normal. Referral for emergency surgical consultation is Laboratory studies show a serum sodium level of obtained. 130 mEq/L (130 mmol/L). Which of the following is the most appropriate initial Which of the following is the most appropriate management? intravenous treatment? (A) Fluid restriction (A) Esmolol (B) Intravenous 0.9% saline (B) Hydralazine (C) 100-mL bolus of 3% saline (C) Nicardipine (D) No treatment (D) Nitroprusside

(A) Fluid restriction (A) Esmolol (B) Intravenous 0.9% saline (B) Hydralazine (C) 100-mL bolus of 3% saline (C) Nicardipine (D) No treatment (D) Nitroprusside 101

Self-Assessment Test rn @ = Item 31 Which of the following is the most appropriate additional > therapy? wn A 65-year-old man is evaluated for fatigue and weak- wn © ness progressing over the last 3 months. His medical (A) Amlodipine n n history is otherwise unremarkable, and he takes no =} (B) Amlodipine-valsartan © medications. = (C) Chlorthalidone aa Findings on physical examination, including vital = signs, are normal. (D) Valsartan Oo wn fa Laboratory studies: Hemoglobin 9 g/dL (90 g/L) Item 33 Albumin 3.0 g/dL (30 g/L) A 43-year-old man is evaluated for one episode of gross Creatinine 0.9 mg/dL (79.6 umol/L) hematuria 3 days ago. He reports no flank pain and no Electrolytes: associated trauma on exertion. Medical history is otherwise Sodium 138 mEq/L (138 mmol/L) unremarkable. He does not smoke cigarettes and takes no Potassium 3.4 mEq/L (3.4 mmol/L) medications. Chloride 118 mEq/L (118 mmol/L) Physical examination findings, including vital signs, Bicarbonate 14 mEq/L (14 mmol/L) are normal. Glucose 74 mg/dL (4.1 mmol/L) Laboratory studies: Phosphorus 2.1 mg/dL (0.7 mmol/L) Blood urea nitrogen Normal Total protein 8.0 g/dL (80 g/L) Creatinine Normal Urinalysis PH 5.0; no blood; no protein; no erythrocytes; 1+ leukocytes; trace Urinalysis No protein; 1+ heme pigment; 10-15 erythrocytes/hpf; glucose 0-2 leukocytes/hpf; no nitrites; no leukocyte esterase Which of the following is the most likely cause of this Random urine protein- 20 mg/g patient’s laboratory findings? creatinine ratio (A) Bartter syndrome Contrast-enhanced CT urogram of the kidneys shows (B) Liddle syndrome no stones, masses, or cysts. (C) Type 1 (hypokalemic distal) renal tubular acidosis Which of the following is the most appropriate diagnostic (D) Type 2 (proximal) renal tubular acidosis test to perform next? (E) Type 4 (hyperkalemic distal) renal tubular (A) Cystoscopy acidosis (B) Kidney biopsy (C) Repeat urinalysis Item 32 (D) 24-Hour urine protein measurement A 46-year-old man is evaluated for confirmed primary hypertension. The patient is asymptomatic and takes Item 34 no medications. He is a current smoker with a 20-pack- year history. Family history is significant for hyperten- A 62-year-old woman comes to the office for kidney trans- sion in his mother and father; his father had a stroke at plantation evaluation. She has end-stage kidney disease. A age 55 years. peritoneal dialysis catheter was placed 2 weeks ago. She also

Self-Assessment Test rn @ = Item 31 Which of the following is the most appropriate additional > therapy? wn A 65-year-old man is evaluated for fatigue and weak- wn © ness progressing over the last 3 months. His medical (A) Amlodipine n n history is otherwise unremarkable, and he takes no =} (B) Amlodipine-valsartan © medications. = (C) Chlorthalidone aa Findings on physical examination, including vital = signs, are normal. (D) Valsartan Oo wn fa Laboratory studies: Hemoglobin 9 g/dL (90 g/L) Item 33 Albumin 3.0 g/dL (30 g/L) A 43-year-old man is evaluated for one episode of gross Creatinine 0.9 mg/dL (79.6 umol/L) hematuria 3 days ago. He reports no flank pain and no Electrolytes: associated trauma on exertion. Medical history is otherwise Sodium 138 mEq/L (138 mmol/L) unremarkable. He does not smoke cigarettes and takes no Potassium 3.4 mEq/L (3.4 mmol/L) medications. Chloride 118 mEq/L (118 mmol/L) Physical examination findings, including vital signs, Bicarbonate 14 mEq/L (14 mmol/L) are normal. Glucose 74 mg/dL (4.1 mmol/L) Laboratory studies: Phosphorus 2.1 mg/dL (0.7 mmol/L) Blood urea nitrogen Normal Total protein 8.0 g/dL (80 g/L) Creatinine Normal Urinalysis PH 5.0; no blood; no protein; no erythrocytes; 1+ leukocytes; trace Urinalysis No protein; 1+ heme pigment; 10-15 erythrocytes/hpf; glucose 0-2 leukocytes/hpf; no nitrites; no leukocyte esterase Which of the following is the most likely cause of this Random urine protein- 20 mg/g patient’s laboratory findings? creatinine ratio (A) Bartter syndrome Contrast-enhanced CT urogram of the kidneys shows (B) Liddle syndrome no stones, masses, or cysts. (C) Type 1 (hypokalemic distal) renal tubular acidosis Which of the following is the most appropriate diagnostic (D) Type 2 (proximal) renal tubular acidosis test to perform next? (E) Type 4 (hyperkalemic distal) renal tubular (A) Cystoscopy acidosis (B) Kidney biopsy (C) Repeat urinalysis Item 32 (D) 24-Hour urine protein measurement A 46-year-old man is evaluated for confirmed primary hypertension. The patient is asymptomatic and takes Item 34 no medications. He is a current smoker with a 20-pack- year history. Family history is significant for hyperten- A 62-year-old woman comes to the office for kidney trans- sion in his mother and father; his father had a stroke at plantation evaluation. She has end-stage kidney disease. A age 55 years. peritoneal dialysis catheter was placed 2 weeks ago. She also On physical examination, blood pressure is 154/96 mm has hypertension. Medications are amlodipine, benazepril,

Self-Assessment Test rn @ = Item 31 Which of the following is the most appropriate additional > therapy? wn A 65-year-old man is evaluated for fatigue and weak- wn © ness progressing over the last 3 months. His medical (A) Amlodipine n n history is otherwise unremarkable, and he takes no =} (B) Amlodipine-valsartan © medications. = (C) Chlorthalidone aa Findings on physical examination, including vital = signs, are normal. (D) Valsartan Oo wn fa Laboratory studies: Hemoglobin 9 g/dL (90 g/L) Item 33 Albumin 3.0 g/dL (30 g/L) A 43-year-old man is evaluated for one episode of gross Creatinine 0.9 mg/dL (79.6 umol/L) hematuria 3 days ago. He reports no flank pain and no Electrolytes: associated trauma on exertion. Medical history is otherwise Sodium 138 mEq/L (138 mmol/L) unremarkable. He does not smoke cigarettes and takes no Potassium 3.4 mEq/L (3.4 mmol/L) medications. Chloride 118 mEq/L (118 mmol/L) Physical examination findings, including vital signs, Bicarbonate 14 mEq/L (14 mmol/L) are normal. Glucose 74 mg/dL (4.1 mmol/L) Laboratory studies: Phosphorus 2.1 mg/dL (0.7 mmol/L) Blood urea nitrogen Normal Total protein 8.0 g/dL (80 g/L) Creatinine Normal Urinalysis PH 5.0; no blood; no protein; no erythrocytes; 1+ leukocytes; trace Urinalysis No protein; 1+ heme pigment; 10-15 erythrocytes/hpf; glucose 0-2 leukocytes/hpf; no nitrites; no leukocyte esterase Which of the following is the most likely cause of this Random urine protein- 20 mg/g patient’s laboratory findings? creatinine ratio (A) Bartter syndrome Contrast-enhanced CT urogram of the kidneys shows (B) Liddle syndrome no stones, masses, or cysts. (C) Type 1 (hypokalemic distal) renal tubular acidosis Which of the following is the most appropriate diagnostic (D) Type 2 (proximal) renal tubular acidosis test to perform next? (E) Type 4 (hyperkalemic distal) renal tubular (A) Cystoscopy acidosis (B) Kidney biopsy (C) Repeat urinalysis Item 32 (D) 24-Hour urine protein measurement A 46-year-old man is evaluated for confirmed primary hypertension. The patient is asymptomatic and takes Item 34 no medications. He is a current smoker with a 20-pack- year history. Family history is significant for hyperten- A 62-year-old woman comes to the office for kidney trans- sion in his mother and father; his father had a stroke at plantation evaluation. She has end-stage kidney disease. A age 55 years. peritoneal dialysis catheter was placed 2 weeks ago. She also On physical examination, blood pressure is 154/96 mm has hypertension. Medications are amlodipine, benazepril, Hg in both arms, pulse rate is 74/min, and respiration rate furosemide, metoprolol, and sodium bicarbonate. is 18/min. BMI is 30. The remainder of the examination is On physical examination, vital signs are normal. A normal. peritoneal dialysis catheter is present. The remainder of the examination is normal. Laboratory studies: Laboratory studies: Fasting lipid profile: Hepatitis B core antibody Positive Total cholesterol 220 mg/dL (5.7 mmol/L) Hepatitis B surface antibody Positive LDL cholesterol 160 mg/dL (4.1 mmol/L) Hepatitis B surface antigen Negative HDL cholesterol 48 mg/dL (1.2 mmol/L) Hepatitis C antibody Positive Creatinine 1.0 mg/dL (88.4 pmol/L) Hepatitis C viral load 2.8 million [U/mL Electrolytes Normal Glucose, fasting 80 mg/dL (4.4 mmol/L) Which of the following is the most appropriate Urinalysis No protein, erythrocytes, or management? leukocytes (A) Avoid antiviral treatment and transplantation A 12-lead ECG is normal. (B) Begin entecavir The patient is instructed in lifestyle modifications, including smoking cessation, exercise, and a low sodium (C) Begin pegylated interferon and ribavirin diet. Moderate-intensity atorvastatin is initiated. (D) Discuss hepatitis C virus treatment and timing

Hg in both arms, pulse rate is 74/min, and respiration rate furosemide, metoprolol, and sodium bicarbonate. is 18/min. BMI is 30. The remainder of the examination is On physical examination, vital signs are normal. A normal. peritoneal dialysis catheter is present. The remainder of the examination is normal. Laboratory studies: Laboratory studies: Fasting lipid profile: Hepatitis B core antibody Positive Total cholesterol 220 mg/dL (5.7 mmol/L) Hepatitis B surface antibody Positive LDL cholesterol 160 mg/dL (4.1 mmol/L) Hepatitis B surface antigen Negative HDL cholesterol 48 mg/dL (1.2 mmol/L) Hepatitis C antibody Positive Creatinine 1.0 mg/dL (88.4 pmol/L) Hepatitis C viral load 2.8 million [U/mL Electrolytes Normal Glucose, fasting 80 mg/dL (4.4 mmol/L) Which of the following is the most appropriate Urinalysis No protein, erythrocytes, or management? leukocytes (A) Avoid antiviral treatment and transplantation A 12-lead ECG is normal. (B) Begin entecavir The patient is instructed in lifestyle modifications, including smoking cessation, exercise, and a low sodium (C) Begin pegylated interferon and ribavirin diet. Moderate-intensity atorvastatin is initiated. (D) Discuss hepatitis C virus treatment and timing 102

ment 1 sheet Item 35 On physical examination, blood pressure is 138/86 mm — cH An 87-year-old man is evaluated in the emergency department Hg; other vital signs are normal. BMI is 32. The remainder of 4 = for a 36-hour history of lower abdominal discomfort, urinary the examination is unremarkable. QB = frequency, and nocturia. He has no other symptoms. Medical Laboratory studies: w wn history is significant for type 2 diabetes mellitus, hypertension, Creatinine 0.9 mg/dL (<8) 72) and IgG4-related autoimmune pancreatitis. Medications are (79.6 umol/L) 1%.) metformin, hydrochlorothiazide, and rituximab. He began Electrolytes Normal = See

= for a 36-hour history of lower abdominal discomfort, urinary the examination is unremarkable. QB = frequency, and nocturia. He has no other symptoms. Medical Laboratory studies: w wn history is significant for type 2 diabetes mellitus, hypertension, Creatinine 0.9 mg/dL (<8) 72) and IgG4-related autoimmune pancreatitis. Medications are (79.6 umol/L) 1%.) metformin, hydrochlorothiazide, and rituximab. He began Electrolytes Normal = See taking over-the-counter chlorpheniramine last week for Urine albumin-creatinine ratio 550 mg/g tf) ” symptoms related to seasonal allergies. Estimated glomerular filtration rate >60 mL/min/1.73 m? On physical examination, he is afebrile. Blood pressure is 158/64 mm Hg, and pulse rate is 78/min. There is ten- Which of the following is the most appropriate treatment? derness to palpation of the lower abdomen. The prostate is (A) Amlodipine diffusely enlarged. (B) Atenolol Laboratory studies show a blood urea nitrogen level of 50 mg/dL (17.9 mmol/L) and a serum creatinine level of (C) Doxazosin 2.4mg/dL (212.2 umol/L). Urinalysis shows a specific gravity (D) Losartan of 1.012, 1+ blood, 1+ protein, 1+ leukocytes, 3 nondysmor- phic erythrocytes/hpf, 1-3 leukocytes/hpf, and no casts. Item 38 Which of the following is the most appropriate initial step A 70-year-old woman is evaluated for right flank pain and in management? dysuria. She has a 20-year history of type 2 diabetes mellitus with neurogenic bladder and recurrent urinary tract infec- (A) Bladder ultrasonography tions. Medications are metformin and simvastatin. (B) Kidney ultrasonography On physical examination, temperature is 38.3 °C (C) MRI of the abdomen and pelvis (100.9 °F); other vital signs are normal. There is tenderness (D) Noncontrast CT of the abdomen and pelvis to palpation over the right flank. The remainder of the examination is normal. Urinalysis shows cloudy urine with a specific gravity of Item 36 1.010, pH of 8.0, 1+ blood, trace protein, 3+ leukocyte esterase, and positive nitrites. Microscopic urinalysis reveals 1-2 eryth- A 38-year-old man is evaluated during a follow-up visit rocytes/hpf, 20-25 leukocytes/hpf, and crystals (shown). for proteinuric chronic kidney disease. Family history is significant for end-stage kidney disease in two uncles and a ee e * b a female cousin. He has no other medical problems, and his only medication is lisinopril. The patient is of African i Seer as Sate oe Lee &. «

taking over-the-counter chlorpheniramine last week for Urine albumin-creatinine ratio 550 mg/g tf) ” symptoms related to seasonal allergies. Estimated glomerular filtration rate >60 mL/min/1.73 m? On physical examination, he is afebrile. Blood pressure is 158/64 mm Hg, and pulse rate is 78/min. There is ten- Which of the following is the most appropriate treatment? derness to palpation of the lower abdomen. The prostate is (A) Amlodipine diffusely enlarged. (B) Atenolol Laboratory studies show a blood urea nitrogen level of 50 mg/dL (17.9 mmol/L) and a serum creatinine level of (C) Doxazosin 2.4mg/dL (212.2 umol/L). Urinalysis shows a specific gravity (D) Losartan of 1.012, 1+ blood, 1+ protein, 1+ leukocytes, 3 nondysmor- phic erythrocytes/hpf, 1-3 leukocytes/hpf, and no casts. Item 38 Which of the following is the most appropriate initial step A 70-year-old woman is evaluated for right flank pain and in management? dysuria. She has a 20-year history of type 2 diabetes mellitus with neurogenic bladder and recurrent urinary tract infec- (A) Bladder ultrasonography tions. Medications are metformin and simvastatin. (B) Kidney ultrasonography On physical examination, temperature is 38.3 °C (C) MRI of the abdomen and pelvis (100.9 °F); other vital signs are normal. There is tenderness (D) Noncontrast CT of the abdomen and pelvis to palpation over the right flank. The remainder of the examination is normal. Urinalysis shows cloudy urine with a specific gravity of Item 36 1.010, pH of 8.0, 1+ blood, trace protein, 3+ leukocyte esterase, and positive nitrites. Microscopic urinalysis reveals 1-2 eryth- A 38-year-old man is evaluated during a follow-up visit rocytes/hpf, 20-25 leukocytes/hpf, and crystals (shown). for proteinuric chronic kidney disease. Family history is significant for end-stage kidney disease in two uncles and a ee e * b a female cousin. He has no other medical problems, and his only medication is lisinopril. The patient is of African i Seer as Sate oe Lee &. « descent. On physical examination, vital signs are normal. There are features of generalized anasarca, with marked edema of

taking over-the-counter chlorpheniramine last week for Urine albumin-creatinine ratio 550 mg/g tf) ” symptoms related to seasonal allergies. Estimated glomerular filtration rate >60 mL/min/1.73 m? On physical examination, he is afebrile. Blood pressure is 158/64 mm Hg, and pulse rate is 78/min. There is ten- Which of the following is the most appropriate treatment? derness to palpation of the lower abdomen. The prostate is (A) Amlodipine diffusely enlarged. (B) Atenolol Laboratory studies show a blood urea nitrogen level of 50 mg/dL (17.9 mmol/L) and a serum creatinine level of (C) Doxazosin 2.4mg/dL (212.2 umol/L). Urinalysis shows a specific gravity (D) Losartan of 1.012, 1+ blood, 1+ protein, 1+ leukocytes, 3 nondysmor- phic erythrocytes/hpf, 1-3 leukocytes/hpf, and no casts. Item 38 Which of the following is the most appropriate initial step A 70-year-old woman is evaluated for right flank pain and in management? dysuria. She has a 20-year history of type 2 diabetes mellitus with neurogenic bladder and recurrent urinary tract infec- (A) Bladder ultrasonography tions. Medications are metformin and simvastatin. (B) Kidney ultrasonography On physical examination, temperature is 38.3 °C (C) MRI of the abdomen and pelvis (100.9 °F); other vital signs are normal. There is tenderness (D) Noncontrast CT of the abdomen and pelvis to palpation over the right flank. The remainder of the examination is normal. Urinalysis shows cloudy urine with a specific gravity of Item 36 1.010, pH of 8.0, 1+ blood, trace protein, 3+ leukocyte esterase, and positive nitrites. Microscopic urinalysis reveals 1-2 eryth- A 38-year-old man is evaluated during a follow-up visit rocytes/hpf, 20-25 leukocytes/hpf, and crystals (shown). for proteinuric chronic kidney disease. Family history is significant for end-stage kidney disease in two uncles and a ee e * b a female cousin. He has no other medical problems, and his only medication is lisinopril. The patient is of African i Seer as Sate oe Lee &. « descent. On physical examination, vital signs are normal. There are features of generalized anasarca, with marked edema of 7. the lower extremities. The remainder of the examination is unremarkable.

taking over-the-counter chlorpheniramine last week for Urine albumin-creatinine ratio 550 mg/g tf) ” symptoms related to seasonal allergies. Estimated glomerular filtration rate >60 mL/min/1.73 m? On physical examination, he is afebrile. Blood pressure is 158/64 mm Hg, and pulse rate is 78/min. There is ten- Which of the following is the most appropriate treatment? derness to palpation of the lower abdomen. The prostate is (A) Amlodipine diffusely enlarged. (B) Atenolol Laboratory studies show a blood urea nitrogen level of 50 mg/dL (17.9 mmol/L) and a serum creatinine level of (C) Doxazosin 2.4mg/dL (212.2 umol/L). Urinalysis shows a specific gravity (D) Losartan of 1.012, 1+ blood, 1+ protein, 1+ leukocytes, 3 nondysmor- phic erythrocytes/hpf, 1-3 leukocytes/hpf, and no casts. Item 38 Which of the following is the most appropriate initial step A 70-year-old woman is evaluated for right flank pain and in management? dysuria. She has a 20-year history of type 2 diabetes mellitus with neurogenic bladder and recurrent urinary tract infec- (A) Bladder ultrasonography tions. Medications are metformin and simvastatin. (B) Kidney ultrasonography On physical examination, temperature is 38.3 °C (C) MRI of the abdomen and pelvis (100.9 °F); other vital signs are normal. There is tenderness (D) Noncontrast CT of the abdomen and pelvis to palpation over the right flank. The remainder of the examination is normal. Urinalysis shows cloudy urine with a specific gravity of Item 36 1.010, pH of 8.0, 1+ blood, trace protein, 3+ leukocyte esterase, and positive nitrites. Microscopic urinalysis reveals 1-2 eryth- A 38-year-old man is evaluated during a follow-up visit rocytes/hpf, 20-25 leukocytes/hpf, and crystals (shown). for proteinuric chronic kidney disease. Family history is significant for end-stage kidney disease in two uncles and a ee e * b a female cousin. He has no other medical problems, and his only medication is lisinopril. The patient is of African i Seer as Sate oe Lee &. « descent. On physical examination, vital signs are normal. There are features of generalized anasarca, with marked edema of 7. the lower extremities. The remainder of the examination is unremarkable. Laboratory studies: a Albumin 2.2 g/dL (22 g/L) ¥ Total cholesterol 264 mg/dL (6.8 mmol/L) +s

Laboratory studies: a Albumin 2.2 g/dL (22 g/L) ¥ Total cholesterol 264 mg/dL (6.8 mmol/L) +s Creatinine 1.8 mg/dL (159.1 umol/L) Urinalysis No blood; 4+ protein Urine protein-creatinine ratio 7850 mg/g Which of the following is the most likely diagnosis? ~~ ~ > : ? v (A) Focal segmental glomerulosclerosis } | 4 ; = (B) Lupus nephritis (C) Membranous nephropathy (D) Minimal change glomerulopathy A Item 37 Infection with which of the following organisms is most A 52-year-old woman is evaluated during a follow-up visit likely? for hypertension management. She has a 10-year history of type 2 diabetes mellitus. Diabetic retinopathy was diag- (A) Escherichia coli nosed 1 year ago. She also has obesity and hyperlipidemia. (B) Proteus mirabilis Medications are hydrochlorothiazide, metformin, empagli- (C) Staphylococcus saprophyticus flozin, and atorvastatin. (D) Streptococcus agalactiae 103

Self-Assessment Test wn @ = Item 39 protein, too numerous to count erythrocytes, and no casts. > Streptococcal rapid antigen test is negative. 7.) A 39-year-old woman is evaluated during a follow-up visit wn @o wn for recently diagnosed stage 2 hypertension confirmed with Which of the following is the most appropriate = home blood pressure monitoring measurements taken over the past month. She also has a 12-year history of type 2 management? Oo =] diabetes mellitus. Medications are metformin and empagli- Fr (A) Amoxicillin flozin. o (B) CT of the abdomen and pelvis wn - On physical examination, blood pressure is 144/92 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. BMI (C) Prednisone is 28. The remainder of the examination unremarkable. (D) Clinical observation Laboratory studies show a serum creatinine level of 0.9 mg/dL (79.6 umol/L), normal electrolyte levels, and a urine albumin-creatinine ratio of 330 mg/g. Item 42 The patient is instructed in lifestyle modifications to A 45-year-old man is evaluated during a routine visit in Sep- control hypertension. tember. He has advanced chronic kidney disease due to IgA nephropathy. Medical history is also significant for chicken- Which of the following is the most appropriate initial pox but with no history of shingles. Medications are carve- therapy? dilol, diltiazem, lisinopril, and sevelamer. His vaccination history includes completion of only required childhood vac- (A) Felodipine cinations and recent COVID-19 immunization. (B) Hydrochlorothiazide Laboratory studies: (C) Hydrochlorothiazide and amlodipine Hepatitis A virus IgM antibody Negative (D) Lisinopril Hepatitis B surface antigen Negative Hepatitis B surface antibody Positive Hepatitis C virus antibody Negative Item 40 Inactivated influenza vaccine is administered. A 38-year-old woman seeks treatment for polyuria and nocturia that began 6 weeks ago after starting lithium for Which of the following is the most appropriate additional bipolar disorder. Medical history is otherwise unremark- vaccine to administer at this visit? able. Her only other medication is olanzapine. Physical examination findings, including vital signs, (A) Hepatitis A vaccine are normal. (B) Hepatitis B vaccine Laboratory studies show a serum sodium level of (C) Herpes zoster recombinant vaccine 145 mEq/L (145 mmol/L) and a urine osmolality of 200 mOsm/kg H,O. (D) Pneumococcal conjugate vaccine (E) Pneumococcal polysaccharide vaccine Which of the following is the most appropriate management? Item 43 (A) Add amiloride A 66-year-old man is evaluated in the hospital for acute (B) Add furosemide kidney injury following percutaneous coronary angiogra- (C) Decrease water intake phy and stent placement 48 hours ago. His medical history (D) Increase protein intake is also significant for hypertension, hyperlipidemia, type 2 diabetes mellitus, and diabetic kidney disease. Medications are lisinopril, hydrochlorothiazide, basal and prandial insu- Item 41 lin, atorvastatin, metoprolol, clopidogrel, and aspirin. A 28-year-old man is evaluated for hematuria that he noted On physical examination, blood pressure is 132/88 mm

wn @ = Item 39 protein, too numerous to count erythrocytes, and no casts. > Streptococcal rapid antigen test is negative. 7.) A 39-year-old woman is evaluated during a follow-up visit wn @o wn for recently diagnosed stage 2 hypertension confirmed with Which of the following is the most appropriate = home blood pressure monitoring measurements taken over the past month. She also has a 12-year history of type 2 management? Oo =] diabetes mellitus. Medications are metformin and empagli- Fr (A) Amoxicillin flozin. o (B) CT of the abdomen and pelvis wn - On physical examination, blood pressure is 144/92 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. BMI (C) Prednisone is 28. The remainder of the examination unremarkable. (D) Clinical observation Laboratory studies show a serum creatinine level of 0.9 mg/dL (79.6 umol/L), normal electrolyte levels, and a urine albumin-creatinine ratio of 330 mg/g. Item 42 The patient is instructed in lifestyle modifications to A 45-year-old man is evaluated during a routine visit in Sep- control hypertension. tember. He has advanced chronic kidney disease due to IgA nephropathy. Medical history is also significant for chicken- Which of the following is the most appropriate initial pox but with no history of shingles. Medications are carve- therapy? dilol, diltiazem, lisinopril, and sevelamer. His vaccination history includes completion of only required childhood vac- (A) Felodipine cinations and recent COVID-19 immunization. (B) Hydrochlorothiazide Laboratory studies: (C) Hydrochlorothiazide and amlodipine Hepatitis A virus IgM antibody Negative (D) Lisinopril Hepatitis B surface antigen Negative Hepatitis B surface antibody Positive Hepatitis C virus antibody Negative Item 40 Inactivated influenza vaccine is administered. A 38-year-old woman seeks treatment for polyuria and nocturia that began 6 weeks ago after starting lithium for Which of the following is the most appropriate additional bipolar disorder. Medical history is otherwise unremark- vaccine to administer at this visit? able. Her only other medication is olanzapine. Physical examination findings, including vital signs, (A) Hepatitis A vaccine are normal. (B) Hepatitis B vaccine Laboratory studies show a serum sodium level of (C) Herpes zoster recombinant vaccine 145 mEq/L (145 mmol/L) and a urine osmolality of 200 mOsm/kg H,O. (D) Pneumococcal conjugate vaccine (E) Pneumococcal polysaccharide vaccine Which of the following is the most appropriate management? Item 43 (A) Add amiloride A 66-year-old man is evaluated in the hospital for acute (B) Add furosemide kidney injury following percutaneous coronary angiogra- (C) Decrease water intake phy and stent placement 48 hours ago. His medical history (D) Increase protein intake is also significant for hypertension, hyperlipidemia, type 2 diabetes mellitus, and diabetic kidney disease. Medications are lisinopril, hydrochlorothiazide, basal and prandial insu- Item 41 lin, atorvastatin, metoprolol, clopidogrel, and aspirin. A 28-year-old man is evaluated for hematuria that he noted On physical examination, blood pressure is 132/88 mm on awakening and a 3-day history of fever, runny nose, and Hg, and pulse rate is 58/min without postural changes. Skin is

wn @ = Item 39 protein, too numerous to count erythrocytes, and no casts. > Streptococcal rapid antigen test is negative. 7.) A 39-year-old woman is evaluated during a follow-up visit wn @o wn for recently diagnosed stage 2 hypertension confirmed with Which of the following is the most appropriate = home blood pressure monitoring measurements taken over the past month. She also has a 12-year history of type 2 management? Oo =] diabetes mellitus. Medications are metformin and empagli- Fr (A) Amoxicillin flozin. o (B) CT of the abdomen and pelvis wn - On physical examination, blood pressure is 144/92 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. BMI (C) Prednisone is 28. The remainder of the examination unremarkable. (D) Clinical observation Laboratory studies show a serum creatinine level of 0.9 mg/dL (79.6 umol/L), normal electrolyte levels, and a urine albumin-creatinine ratio of 330 mg/g. Item 42 The patient is instructed in lifestyle modifications to A 45-year-old man is evaluated during a routine visit in Sep- control hypertension. tember. He has advanced chronic kidney disease due to IgA nephropathy. Medical history is also significant for chicken- Which of the following is the most appropriate initial pox but with no history of shingles. Medications are carve- therapy? dilol, diltiazem, lisinopril, and sevelamer. His vaccination history includes completion of only required childhood vac- (A) Felodipine cinations and recent COVID-19 immunization. (B) Hydrochlorothiazide Laboratory studies: (C) Hydrochlorothiazide and amlodipine Hepatitis A virus IgM antibody Negative (D) Lisinopril Hepatitis B surface antigen Negative Hepatitis B surface antibody Positive Hepatitis C virus antibody Negative Item 40 Inactivated influenza vaccine is administered. A 38-year-old woman seeks treatment for polyuria and nocturia that began 6 weeks ago after starting lithium for Which of the following is the most appropriate additional bipolar disorder. Medical history is otherwise unremark- vaccine to administer at this visit? able. Her only other medication is olanzapine. Physical examination findings, including vital signs, (A) Hepatitis A vaccine are normal. (B) Hepatitis B vaccine Laboratory studies show a serum sodium level of (C) Herpes zoster recombinant vaccine 145 mEq/L (145 mmol/L) and a urine osmolality of 200 mOsm/kg H,O. (D) Pneumococcal conjugate vaccine (E) Pneumococcal polysaccharide vaccine Which of the following is the most appropriate management? Item 43 (A) Add amiloride A 66-year-old man is evaluated in the hospital for acute (B) Add furosemide kidney injury following percutaneous coronary angiogra- (C) Decrease water intake phy and stent placement 48 hours ago. His medical history (D) Increase protein intake is also significant for hypertension, hyperlipidemia, type 2 diabetes mellitus, and diabetic kidney disease. Medications are lisinopril, hydrochlorothiazide, basal and prandial insu- Item 41 lin, atorvastatin, metoprolol, clopidogrel, and aspirin. A 28-year-old man is evaluated for hematuria that he noted On physical examination, blood pressure is 132/88 mm on awakening and a 3-day history of fever, runny nose, and Hg, and pulse rate is 58/min without postural changes. Skin is cough. One year ago, he had an episode of gross hematuria warm and dry. The remainder of the examination is normal. after running a half marathon. Evaluation at that time Laboratory studies: resulted in a biopsy diagnosis of IgA nephropathy. He has Hematocrit 36% no other medical problems and takes no medications. Platelet count 127,000/uL (127 x 10°/L) On physical examination, temperature is 37.9 °C Blood urea nitrogen 54 mg/dL (19.3 mmol/L) (100.2 °F), and blood pressure is 110/70 mm Hg; other vital Creatinine 3.6 mg/dL (318.2 umol/L); signs are normal. The nasal mucosa is edematous, with on admission, 3.3 mg/dL serous discharge. Examination of the oropharynx reveals (291.7 umol/L) erythema without exudate. There is no lymphadenopathy. Urinalysis Specific gravity 1.010; pH Lungs are clear to auscultation. The remainder of the exam- 5.5; trace protein; trace ination is unremarkable. leukocytes; 1-3 erythrocytes/ Laboratory studies show a serum creatinine level of hpf; 1-3 leukocytes/hpf; 3-5 0.9 mg/dL (79.6 umol/L); urinalysis shows 3+ blood, trace granular casts/hpf

cough. One year ago, he had an episode of gross hematuria warm and dry. The remainder of the examination is normal. after running a half marathon. Evaluation at that time Laboratory studies: resulted in a biopsy diagnosis of IgA nephropathy. He has Hematocrit 36% no other medical problems and takes no medications. Platelet count 127,000/uL (127 x 10°/L) On physical examination, temperature is 37.9 °C Blood urea nitrogen 54 mg/dL (19.3 mmol/L) (100.2 °F), and blood pressure is 110/70 mm Hg; other vital Creatinine 3.6 mg/dL (318.2 umol/L); signs are normal. The nasal mucosa is edematous, with on admission, 3.3 mg/dL serous discharge. Examination of the oropharynx reveals (291.7 umol/L) erythema without exudate. There is no lymphadenopathy. Urinalysis Specific gravity 1.010; pH Lungs are clear to auscultation. The remainder of the exam- 5.5; trace protein; trace ination is unremarkable. leukocytes; 1-3 erythrocytes/ Laboratory studies show a serum creatinine level of hpf; 1-3 leukocytes/hpf; 3-5 0.9 mg/dL (79.6 umol/L); urinalysis shows 3+ blood, trace granular casts/hpf 104

_ Self Astasamant Test ut o Kidney ultrasound shows a 10.5-cm right kidney, Kidney ultrasound shows kidneys of normal size and — he? 11.3-cm left kidney, and normal cortical echogenicity; there echogenicity. & CONT. is no hydronephrosis. Which of the following is the most appropriate diagnostic S wn wn Which of the following is the most likely diagnosis? test to perform next? wy wn 17) Acute tubular necrosis (A) Erythrocyte sedimentation rate m4 (A) = (B) Atheroembolic-induced acute kidney injury (B) Extractable nuclear antigen panel c-F) rn (C) Hemolytic uremic syndrome (C) Kidney biopsy (D) Prerenal acute kidney injury (D) Skin biopsy

Acute tubular necrosis (A) Erythrocyte sedimentation rate m4 (A) = (B) Atheroembolic-induced acute kidney injury (B) Extractable nuclear antigen panel c-F) rn (C) Hemolytic uremic syndrome (C) Kidney biopsy (D) Prerenal acute kidney injury (D) Skin biopsy Item 44 Item 46 A 45-year-old woman is evaluated in the emergency depart- A 74-year-old woman is evaluated during a follow-up ment after ingesting 50 aspirin. She is alert and reports visit for hypertension and slowly progressive chronic symptoms of nausea and tinnitus. Activated charcoal is kidney disease. She reports that she feels well and has administered. no symptoms. Medications are atenolol, cholecalciferol, On physical examination, the patient is afebrile. Blood hydralazine, nifedipine, simvastatin, and sodium bicar- pressure is 130/70 mm Hg, pulse rate is 92/min, and respi- bonate. ration rate is 32/min. The remainder of the examination is On physical examination, blood pressure is 130/70 mm normal. Hg; other vital signs are normal. The remainder of the exam- Laboratory studies: ination is unremarkable. Creatinine 0.9 mg/dL (79.6 umol/L) Laboratory studies show an estimated glomerular fil- Electrolytes: tration rate of 28 mL/min/1.73 m?. Sodium 139 mEq/L (139 mmol/L) Potassium 4.0 mEq/L (4.0 mmol/L) Which of the following is the most appropriate Chloride 91 mEq/L (91 mmol/L) management? Bicarbonate 14 mEq/L (14 mmol/L) (A) Arteriovenous fistula placement evaluation Arterial blood gases: pH 7.45 (B) Dialysis initiation Pco, 21 mm Hg (2.8 kPa) (C) Kidney transplant evaluation Salicylate 65 ug/mL (470 pmol/L) (D) Renal replacement therapy education

Item 44 Item 46 A 45-year-old woman is evaluated in the emergency depart- A 74-year-old woman is evaluated during a follow-up ment after ingesting 50 aspirin. She is alert and reports visit for hypertension and slowly progressive chronic symptoms of nausea and tinnitus. Activated charcoal is kidney disease. She reports that she feels well and has administered. no symptoms. Medications are atenolol, cholecalciferol, On physical examination, the patient is afebrile. Blood hydralazine, nifedipine, simvastatin, and sodium bicar- pressure is 130/70 mm Hg, pulse rate is 92/min, and respi- bonate. ration rate is 32/min. The remainder of the examination is On physical examination, blood pressure is 130/70 mm normal. Hg; other vital signs are normal. The remainder of the exam- Laboratory studies: ination is unremarkable. Creatinine 0.9 mg/dL (79.6 umol/L) Laboratory studies show an estimated glomerular fil- Electrolytes: tration rate of 28 mL/min/1.73 m?. Sodium 139 mEq/L (139 mmol/L) Potassium 4.0 mEq/L (4.0 mmol/L) Which of the following is the most appropriate Chloride 91 mEq/L (91 mmol/L) management? Bicarbonate 14 mEq/L (14 mmol/L) (A) Arteriovenous fistula placement evaluation Arterial blood gases: pH 7.45 (B) Dialysis initiation Pco, 21 mm Hg (2.8 kPa) (C) Kidney transplant evaluation Salicylate 65 ug/mL (470 pmol/L) (D) Renal replacement therapy education Which of the following is the most appropriate treatment?

Item 44 Item 46 A 45-year-old woman is evaluated in the emergency depart- A 74-year-old woman is evaluated during a follow-up ment after ingesting 50 aspirin. She is alert and reports visit for hypertension and slowly progressive chronic symptoms of nausea and tinnitus. Activated charcoal is kidney disease. She reports that she feels well and has administered. no symptoms. Medications are atenolol, cholecalciferol, On physical examination, the patient is afebrile. Blood hydralazine, nifedipine, simvastatin, and sodium bicar- pressure is 130/70 mm Hg, pulse rate is 92/min, and respi- bonate. ration rate is 32/min. The remainder of the examination is On physical examination, blood pressure is 130/70 mm normal. Hg; other vital signs are normal. The remainder of the exam- Laboratory studies: ination is unremarkable. Creatinine 0.9 mg/dL (79.6 umol/L) Laboratory studies show an estimated glomerular fil- Electrolytes: tration rate of 28 mL/min/1.73 m?. Sodium 139 mEq/L (139 mmol/L) Potassium 4.0 mEq/L (4.0 mmol/L) Which of the following is the most appropriate Chloride 91 mEq/L (91 mmol/L) management? Bicarbonate 14 mEq/L (14 mmol/L) (A) Arteriovenous fistula placement evaluation Arterial blood gases: pH 7.45 (B) Dialysis initiation Pco, 21 mm Hg (2.8 kPa) (C) Kidney transplant evaluation Salicylate 65 ug/mL (470 pmol/L) (D) Renal replacement therapy education Which of the following is the most appropriate treatment? (A) Acetazolamide Item 47 (B) Hemodialysis A 72-year-old man is evaluated for an ulcerating, painful (C) Intravenous 0.9% saline lesion on his left calf that began as a patch of red skin 2 to 3 weeks ago. He has dialysis-dependent end-stage kid- (D) Intravenous sodium bicarbonate ney disease, atrial fibrillation, and hypertension. Medica- tions are amlodipine, calcium acetate, calcitriol, insulin, and warfarin. There have been no recent changes in his Item 45 medications. A 19-year-old woman is evaluated for a 2-week history of On physical examination, vital signs are normal. Skin fatigue, poor appetite, arthralgia of the hands and knees, findings are shown. There are no other skin changes, lesions, and a rash, all of which appeared 1 day after a trip to the or rash. beach. She has no other medical problems and takes no medications. On physical examination, vital signs are normal. A malar rash characterized by pink-violet papules and plaques with sparing of the nasolabial folds is noted. The remainder of the examination, including joint examination, is normal. Laboratory studies: Albumin 3.1 g/dL (31 g/L) C3 50 mg/dL (500 mg/L) C4 9 mg/dL (90 mg/L) Creatinine 1.1 mg/dL (97.2 umol/L) Antinuclear antibodies Titer, 1:160 Urinalysis 3+ blood; 3+ protein; many erythrocytes; occasional dysmorphic erythrocytes; rare erythrocyte casts

(A) Acetazolamide Item 47 (B) Hemodialysis A 72-year-old man is evaluated for an ulcerating, painful (C) Intravenous 0.9% saline lesion on his left calf that began as a patch of red skin 2 to 3 weeks ago. He has dialysis-dependent end-stage kid- (D) Intravenous sodium bicarbonate ney disease, atrial fibrillation, and hypertension. Medica- tions are amlodipine, calcium acetate, calcitriol, insulin, and warfarin. There have been no recent changes in his Item 45 medications. A 19-year-old woman is evaluated for a 2-week history of On physical examination, vital signs are normal. Skin fatigue, poor appetite, arthralgia of the hands and knees, findings are shown. There are no other skin changes, lesions, and a rash, all of which appeared 1 day after a trip to the or rash. beach. She has no other medical problems and takes no medications. On physical examination, vital signs are normal. A malar rash characterized by pink-violet papules and plaques with sparing of the nasolabial folds is noted. The remainder of the examination, including joint examination, is normal. Laboratory studies: Albumin 3.1 g/dL (31 g/L) C3 50 mg/dL (500 mg/L) C4 9 mg/dL (90 mg/L) Creatinine 1.1 mg/dL (97.2 umol/L) Antinuclear antibodies Titer, 1:160 Urinalysis 3+ blood; 3+ protein; many erythrocytes; occasional dysmorphic erythrocytes; rare erythrocyte casts 105

Selt-Aesesemant Test 7) 2 = Laboratory studies: Estimated glomerular 56 mL/min/1.73 m? > wn INR 25 filtration rate wn ro) Calcium 9.6 mg/dL (2.4 mmol/L) Urinalysis Specific gravity 1.020; pH 5.0; wn wn Phosphorus 3.1 mg/dL (1.0 mmol/L) no blood; no leukocytes; no 3 Parathyroid hormone 361 pg/mL (361 ng/L) ketones © = Urine sodium 45 mEq/L (45 mmol/L) rr A skin punch biopsy shows calcifications in the sub- = Urine potassium 10 mEq/L (10 mmol/L) © cutaneous tissue within necrotic lipocytes and within the wn Urine chloride 40 mEq/L (40 mmol/L) - walls of small blood vessels. There is confluent epidermal necrosis. Which of the following is the most likely cause of this patient’s hyperkalemia? Which of the following is the most likely diagnosis? (A) Atenolol (A) Calciphylaxis ( B) Chronic kidney disease (B) Leukocytoclastic vasculitis ( C) Diarrhea (C) Venous stasis ulcer ( D) Type 1 (hypokalemic distal) renal tubular acidosis (D) Warfarin skin necrosis (E) Type 4 (hyperkalemic distal) renal tubular acidosis

Selt-Aesesemant Test 7) 2 = Laboratory studies: Estimated glomerular 56 mL/min/1.73 m? > wn INR 25 filtration rate wn ro) Calcium 9.6 mg/dL (2.4 mmol/L) Urinalysis Specific gravity 1.020; pH 5.0; wn wn Phosphorus 3.1 mg/dL (1.0 mmol/L) no blood; no leukocytes; no 3 Parathyroid hormone 361 pg/mL (361 ng/L) ketones © = Urine sodium 45 mEq/L (45 mmol/L) rr A skin punch biopsy shows calcifications in the sub- = Urine potassium 10 mEq/L (10 mmol/L) © cutaneous tissue within necrotic lipocytes and within the wn Urine chloride 40 mEq/L (40 mmol/L) - walls of small blood vessels. There is confluent epidermal necrosis. Which of the following is the most likely cause of this patient’s hyperkalemia? Which of the following is the most likely diagnosis? (A) Atenolol (A) Calciphylaxis ( B) Chronic kidney disease (B) Leukocytoclastic vasculitis ( C) Diarrhea (C) Venous stasis ulcer ( D) Type 1 (hypokalemic distal) renal tubular acidosis (D) Warfarin skin necrosis (E) Type 4 (hyperkalemic distal) renal tubular acidosis Item 48 Item 50 A 27-year-old woman is evaluated for hypertension. At her routine visit 6 months ago, her blood pressure was A 42-year-old man is evaluated for a 4-month history of 120/76 mm Hg. There is no family history of hyperten- elevated blood pressure. He has attempted lifestyle mod- sion. She has no other medical problems and takes no ification but has been unable to lower his blood pressure. medications. His medical history is otherwise unremarkable. The patient On physical examination, blood pressure is 146/92 mm takes no medications. He is Black. Hg in the right arm and 148/94 mm Hg in the left arm; pulse On physical examination, blood pressure is 148/94 mm rate is 68/min. A systolic-diastolic abdominal bruit over the Hg, and pulse rate is 74/min. BMI is 24. The remainder of the right lower quadrant is heard. The remainder of the exam- examination is normal. ination is unremarkable. Laboratory studies: Laboratory studies: Creatinine 1.1 mg/dL (97.2 umol/L) Bicarbonate 24 mEq/L (24 mmol/L) Electrolytes Normal Creatinine 0.8 mg/dL (70.7 umol/L) Urine albumin-creatinine ratio Undetectable Potassium 4,2 mEq/L (4.2 mmol/L) Estimated glomerular filtration >60 mL/min/1.73 m2 Sodium 140 mEq/L (140 mmol/L) rate

Item 48 Item 50 A 27-year-old woman is evaluated for hypertension. At her routine visit 6 months ago, her blood pressure was A 42-year-old man is evaluated for a 4-month history of 120/76 mm Hg. There is no family history of hyperten- elevated blood pressure. He has attempted lifestyle mod- sion. She has no other medical problems and takes no ification but has been unable to lower his blood pressure. medications. His medical history is otherwise unremarkable. The patient On physical examination, blood pressure is 146/92 mm takes no medications. He is Black. Hg in the right arm and 148/94 mm Hg in the left arm; pulse On physical examination, blood pressure is 148/94 mm rate is 68/min. A systolic-diastolic abdominal bruit over the Hg, and pulse rate is 74/min. BMI is 24. The remainder of the right lower quadrant is heard. The remainder of the exam- examination is normal. ination is unremarkable. Laboratory studies: Laboratory studies: Creatinine 1.1 mg/dL (97.2 umol/L) Bicarbonate 24 mEq/L (24 mmol/L) Electrolytes Normal Creatinine 0.8 mg/dL (70.7 umol/L) Urine albumin-creatinine ratio Undetectable Potassium 4,2 mEq/L (4.2 mmol/L) Estimated glomerular filtration >60 mL/min/1.73 m2 Sodium 140 mEq/L (140 mmol/L) rate Urinalysis No blood or protein A 12-lead ECG shows normal sinus rhythm, no axis, Pregnancy test Negative and no evidence of left ventricular hypertrophy.

Item 48 Item 50 A 27-year-old woman is evaluated for hypertension. At her routine visit 6 months ago, her blood pressure was A 42-year-old man is evaluated for a 4-month history of 120/76 mm Hg. There is no family history of hyperten- elevated blood pressure. He has attempted lifestyle mod- sion. She has no other medical problems and takes no ification but has been unable to lower his blood pressure. medications. His medical history is otherwise unremarkable. The patient On physical examination, blood pressure is 146/92 mm takes no medications. He is Black. Hg in the right arm and 148/94 mm Hg in the left arm; pulse On physical examination, blood pressure is 148/94 mm rate is 68/min. A systolic-diastolic abdominal bruit over the Hg, and pulse rate is 74/min. BMI is 24. The remainder of the right lower quadrant is heard. The remainder of the exam- examination is normal. ination is unremarkable. Laboratory studies: Laboratory studies: Creatinine 1.1 mg/dL (97.2 umol/L) Bicarbonate 24 mEq/L (24 mmol/L) Electrolytes Normal Creatinine 0.8 mg/dL (70.7 umol/L) Urine albumin-creatinine ratio Undetectable Potassium 4,2 mEq/L (4.2 mmol/L) Estimated glomerular filtration >60 mL/min/1.73 m2 Sodium 140 mEq/L (140 mmol/L) rate Urinalysis No blood or protein A 12-lead ECG shows normal sinus rhythm, no axis, Pregnancy test Negative and no evidence of left ventricular hypertrophy. Which of the following is the most appropriate diagnostic test to perform next? In addition to continuing therapeutic lifestyle interventions, which of the following is the most (A) Plasma aldosterone concentration/plasma renin appropriate treatment? activity ratio (A) Amlodipine (B) Plasma fractionated metanephrines (B) Lisinopril (C) Renal artery CT angiography (C) Losartan (D) Urine albumin-creatinine ratio (D) Metoprolol

Which of the following is the most appropriate diagnostic test to perform next? In addition to continuing therapeutic lifestyle interventions, which of the following is the most (A) Plasma aldosterone concentration/plasma renin appropriate treatment? activity ratio (A) Amlodipine (B) Plasma fractionated metanephrines (B) Lisinopril (C) Renal artery CT angiography (C) Losartan (D) Urine albumin-creatinine ratio (D) Metoprolol Item 49 A 55-year-old man is evaluated for a 4-month history of Item 51 persistent hyperkalemia and intermittent diarrhea. Med- A 45-year-old man is evaluated in the emergency ical history is significant for long-standing type 2 diabetes department for painful myalgia of his legs and difficulty mellitus and hypertension. Medications are metformin, walking after running in a 10-kilometer race. Since the atorvastatin, atenolol, and amlodipine. race, he has had minimal output of dark brown urine. Physical examination findings, including vital signs, He has hyperlipidemia treated with high-intensity atorva- are normal. statin. Laboratory studies: On physical examination, temperature is 37.7 °C Electrolytes: (99.9 °F), blood pressure is 112/67 mm Hg, and pulse rate Sodium 138 mEq/L (138 mmol/L) is 88/min. Mucosae are dry, and skin turgor is dimin- Potassium 5.3 mEq/L (5.3 mmol/L) ished. The muscles of the upper and lower extremities are Chloride 112 mEq/L (112 mmol/L) tender to palpation. The remainder of the examination is Bicarbonate 18 mEq/L (18 mmol/L) normal. 106

__Sal}-Assasement Test al Laboratory studies: Previous evaluation revealed no evidence of retinopa- od — Calcium 7.5 mg/dL (1.9 mmol/L) thy, left ventricular hypertrophy, or kidney disease. ned cd CONT. Creatine kinase 57,000 U/L a

Calcium 7.5 mg/dL (1.9 mmol/L) thy, left ventricular hypertrophy, or kidney disease. ned cd CONT. Creatine kinase 57,000 U/L a Creatinine 1.5 mg/dL (132.6 umol/L) = Which of the following is the most appropriate wn Electrolytes: management? wn iF) Sodium 137 mEq/L (137 mmol/L) “a wn (A) Discontinue ramipril Potassium 5.3 mEq/L (5.3 mmol/L) = Chloride 104 mEq/L (104 mmol/L) (B) Discontinue ramipril; start hydralazine = CF Bicarbonate 19 mEq/L (19 mmol/L) (C) Discontinue ramipril; start spironolactone ia)

Creatinine 1.5 mg/dL (132.6 umol/L) = Which of the following is the most appropriate wn Electrolytes: management? wn iF) Sodium 137 mEq/L (137 mmol/L) “a wn (A) Discontinue ramipril Potassium 5.3 mEq/L (5.3 mmol/L) = Chloride 104 mEq/L (104 mmol/L) (B) Discontinue ramipril; start hydralazine = CF Bicarbonate 19 mEq/L (19 mmol/L) (C) Discontinue ramipril; start spironolactone ia) Phosphorus 6.3 mg/dL (2.0 mmol/L) (D) No change in therapy Urate 9.4 mg/dL (0.55 mmol/L) Urinalysis Specific gravity 1.012; pH 5.5; 3+ blood; trace protein; 1-2 erythrocytes/hpf and pigmented Item 54 granular casts/hpf A 46-year-old man is evaluated in the emergency depart- ment for right flank and abdominal pain that began several Which of the following is the most likely cause of this hours ago. Medical history is significant for hypertension, patient’s findings? type 2 diabetes mellitus, hyperlipidemia, and obesity. He

Phosphorus 6.3 mg/dL (2.0 mmol/L) (D) No change in therapy Urate 9.4 mg/dL (0.55 mmol/L) Urinalysis Specific gravity 1.012; pH 5.5; 3+ blood; trace protein; 1-2 erythrocytes/hpf and pigmented Item 54 granular casts/hpf A 46-year-old man is evaluated in the emergency depart- ment for right flank and abdominal pain that began several Which of the following is the most likely cause of this hours ago. Medical history is significant for hypertension, patient’s findings? type 2 diabetes mellitus, hyperlipidemia, and obesity. He (A) Immune-mediated necrotizing myopathy has no history of kidney stones. Medications are losartan, rosuvastatin, and metformin. (B) Inflammatory myopathy On physical examination, vital signs are normal. BMI is (C) March hemoglobinuria 32. The patient appears uncomfortable. The remainder of the (D) Rhabdomyolysis examination is unremarkable.

(A) Immune-mediated necrotizing myopathy has no history of kidney stones. Medications are losartan, rosuvastatin, and metformin. (B) Inflammatory myopathy On physical examination, vital signs are normal. BMI is (C) March hemoglobinuria 32. The patient appears uncomfortable. The remainder of the (D) Rhabdomyolysis examination is unremarkable. Laboratory studies: Calcium 9.6 mg/dL (2.4 mmol/L) Item 52 Creatinine 1.4 mg/dL (123.8 umol/L) A 46-year-old man comes to the office to discuss results Electrolytes: of his home blood pressure monitoring. His average blood Sodium 139 mEq/L (139 mmol/L) pressure measurement for the past month is 136/84 mm Potassium 4.4 mEq/L (4.4 mmol/L) Hg. Based on his blood pressure measurements, previously Chloride 104 mEq/L (104 mmol/L) measured lipid levels, current history of cigarette smoking, Bicarbonate 24 mEq/L (24 mmol/L) and Black race, his 10-year atherosclerotic cardiovascular Urinalysis Specific gravity 1.018; pH 5.0; 2+ blood; disease event risk is calculated to be 10.3%. Recent labora- no leukocyte esterase; no nitrites; 10-20 tory studies showed his serum creatinine, blood glucose, erythrocytes/hpf; 1-3 leukocytes/hpf electrolytes, and urinalysis were normal. An ECG was nor- mal. The patient is asymptomatic and takes no medications. Noncontrast helical CT scan of the abdomen shows a On physical examination, blood pressure is 134/84 mm 5-mm stone at the right ureteropelvic junction. Hounsfield Hg in both arms; other vital signs are normal. BMI is 30. The units are compatible with a uric acid stone.

Laboratory studies: Calcium 9.6 mg/dL (2.4 mmol/L) Item 52 Creatinine 1.4 mg/dL (123.8 umol/L) A 46-year-old man comes to the office to discuss results Electrolytes: of his home blood pressure monitoring. His average blood Sodium 139 mEq/L (139 mmol/L) pressure measurement for the past month is 136/84 mm Potassium 4.4 mEq/L (4.4 mmol/L) Hg. Based on his blood pressure measurements, previously Chloride 104 mEq/L (104 mmol/L) measured lipid levels, current history of cigarette smoking, Bicarbonate 24 mEq/L (24 mmol/L) and Black race, his 10-year atherosclerotic cardiovascular Urinalysis Specific gravity 1.018; pH 5.0; 2+ blood; disease event risk is calculated to be 10.3%. Recent labora- no leukocyte esterase; no nitrites; 10-20 tory studies showed his serum creatinine, blood glucose, erythrocytes/hpf; 1-3 leukocytes/hpf electrolytes, and urinalysis were normal. An ECG was nor- mal. The patient is asymptomatic and takes no medications. Noncontrast helical CT scan of the abdomen shows a On physical examination, blood pressure is 134/84 mm 5-mm stone at the right ureteropelvic junction. Hounsfield Hg in both arms; other vital signs are normal. BMI is 30. The units are compatible with a uric acid stone. remainder of the examination is normal. The patient is instructed on the implementation of Which of the following is the most appropriate treatment? therapeutic lifestyle modifications, including weight loss, (A) Allopurinol heart-healthy diet, dietary sodium restriction, exercise, and smoking cessation. (B) Lithotripsy (C) Potassium citrate Which of the following is the most appropriate additional (D) Tamsulosin management?

remainder of the examination is normal. The patient is instructed on the implementation of Which of the following is the most appropriate treatment? therapeutic lifestyle modifications, including weight loss, (A) Allopurinol heart-healthy diet, dietary sodium restriction, exercise, and smoking cessation. (B) Lithotripsy (C) Potassium citrate Which of the following is the most appropriate additional (D) Tamsulosin management? (A) Reassess blood pressure in 3 months Item 55 (B) Start amlodipine A 49-year-old woman is evaluated during a routine follow-up (C) Start chlorthalidone and losartan visit. Medical history is significant for chronic kidney dis- (D) Start lisinopril ease, hypertension, and HIV infection. She has been taking her current antihypertensive medications for 6 years. Her antiretroviral regimen was changed 6 weeks ago to a more Item 53 convenient once-daily dosing regimen. Current medica- A 28-year-old woman seeks preconception counseling. She tions are dolutegravir-abacavir-lamivudine and lisinopril- has a 3-year history of primary hypertension. Medical his- hydrochlorothiazide. tory is otherwise unremarkable, and her only medication Findings on physical examination, including vital is ramipril. signs, are normal. On physical examination, blood pressure is 138/78 mm Laboratory studies performed 2 weeks ago showed a Hg. Average blood pressure with home blood pressure mon- continued suppressed viral load and a serum creatinine itoring is 126/72 mm Hg. Other vital signs are normal. BMI is level increase from her baseline of 1.2 mg/dL to 1.6 mg/dL 30. The remainder of the examination is normal. (106.1-141.4 umol/L).

(A) Reassess blood pressure in 3 months Item 55 (B) Start amlodipine A 49-year-old woman is evaluated during a routine follow-up (C) Start chlorthalidone and losartan visit. Medical history is significant for chronic kidney dis- (D) Start lisinopril ease, hypertension, and HIV infection. She has been taking her current antihypertensive medications for 6 years. Her antiretroviral regimen was changed 6 weeks ago to a more Item 53 convenient once-daily dosing regimen. Current medica- A 28-year-old woman seeks preconception counseling. She tions are dolutegravir-abacavir-lamivudine and lisinopril- has a 3-year history of primary hypertension. Medical his- hydrochlorothiazide. tory is otherwise unremarkable, and her only medication Findings on physical examination, including vital is ramipril. signs, are normal. On physical examination, blood pressure is 138/78 mm Laboratory studies performed 2 weeks ago showed a Hg. Average blood pressure with home blood pressure mon- continued suppressed viral load and a serum creatinine itoring is 126/72 mm Hg. Other vital signs are normal. BMI is level increase from her baseline of 1.2 mg/dL to 1.6 mg/dL 30. The remainder of the examination is normal. (106.1-141.4 umol/L). 107

Self-Assessment Test 2) = =- Today’s laboratory studies: Which of the following is the most likely cause of this > wv Creatinine 1.6 mg/dL (141.4 umol/L) patient’s hypernatremia? 7) @ Urinalysis No blood, protein, or erythrocytes wn (A) Diabetes insipidus a) Urine albumin- 100 mg/g (unchanged from baseline) 3 creatinine ratio (B) Electrolyte diuresis © 5 (C) Glucose diuresis - Which of the following is the most appropriate (D) Urea diuresis o management? ”~ vr

2) = =- Today’s laboratory studies: Which of the following is the most likely cause of this > wv Creatinine 1.6 mg/dL (141.4 umol/L) patient’s hypernatremia? 7) @ Urinalysis No blood, protein, or erythrocytes wn (A) Diabetes insipidus a) Urine albumin- 100 mg/g (unchanged from baseline) 3 creatinine ratio (B) Electrolyte diuresis © 5 (C) Glucose diuresis - Which of the following is the most appropriate (D) Urea diuresis o management? ”~ vr (A) Discontinue lisinopril-hydrochlorothiazide Item 58 (B) Measure 24-hour urine creatinine clearance A 61-year-old man is evaluated for bilateral action tremor (C) Return to prior antiretroviral regimen of the hands and rarely the feet that began 7 days ago. The (D) No further management is indicated intensity of the tremor varies and is worse in the morning and late afternoon. He has no other symptoms. There is no family history of tremor or Parkinson disease. Four months Item 56 ago, he underwent living-donor related kidney transplan- A 44-year-old woman is evaluated during a follow-up visit tation. Medical history is also significant for hypertension. for chronic hypertension. Over the past month, her aver- Medications are atorvastatin, lisinopril, metoprolol, myco- age blood pressure measured with home blood pressure phenolate mofetil, nifedipine, prednisone, sulfamethoxazole- monitoring was 150/90 mm Hg. There is no family history trimethoprim, tacrolimus, and valganciclovir. of hypertension. She has no other medical problems. The On physical examination, vital signs are normal. There patient adheres to a low sodium diet. Medications are maxi- is bilateral tremor of the hands present when the hands are mum doses of amlodipine, atenolol, and lisinopril. resting in the lap, with outstretched arms, and with various On physical examination, blood pressure is 150/96 mm actions. The remainder of the examination is normal. Hg, and pulse rate is 64/min; other vital signs are normal. Laboratory studies show a serum creatinine level of BMI is 26. The remainder of the examination is unremark- 1.2 mg/dL (106.1 umol/L). able. Laboratory studies show a serum creatinine level of Which of the following is the most likely medication 0.8 mg/dL (70.7 pmol/L) and normal electrolyte levels. Uri- responsible for this patient’s tremor? nalysis shows no blood, protein, or leukocyte esterase. (A) Metoprolol

(A) Discontinue lisinopril-hydrochlorothiazide Item 58 (B) Measure 24-hour urine creatinine clearance A 61-year-old man is evaluated for bilateral action tremor (C) Return to prior antiretroviral regimen of the hands and rarely the feet that began 7 days ago. The (D) No further management is indicated intensity of the tremor varies and is worse in the morning and late afternoon. He has no other symptoms. There is no family history of tremor or Parkinson disease. Four months Item 56 ago, he underwent living-donor related kidney transplan- A 44-year-old woman is evaluated during a follow-up visit tation. Medical history is also significant for hypertension. for chronic hypertension. Over the past month, her aver- Medications are atorvastatin, lisinopril, metoprolol, myco- age blood pressure measured with home blood pressure phenolate mofetil, nifedipine, prednisone, sulfamethoxazole- monitoring was 150/90 mm Hg. There is no family history trimethoprim, tacrolimus, and valganciclovir. of hypertension. She has no other medical problems. The On physical examination, vital signs are normal. There patient adheres to a low sodium diet. Medications are maxi- is bilateral tremor of the hands present when the hands are mum doses of amlodipine, atenolol, and lisinopril. resting in the lap, with outstretched arms, and with various On physical examination, blood pressure is 150/96 mm actions. The remainder of the examination is normal. Hg, and pulse rate is 64/min; other vital signs are normal. Laboratory studies show a serum creatinine level of BMI is 26. The remainder of the examination is unremark- 1.2 mg/dL (106.1 umol/L). able. Laboratory studies show a serum creatinine level of Which of the following is the most likely medication 0.8 mg/dL (70.7 pmol/L) and normal electrolyte levels. Uri- responsible for this patient’s tremor? nalysis shows no blood, protein, or leukocyte esterase. (A) Metoprolol Which of the following is the most appropriate next step in (B) Mycophenolate mofetil management? (C) Prednisone (D) Tacrolimus (A) Add chlorthalidone (B) Measure plasma aldosterone concentration/plasma renin activity ratio Item 59 (C) Measure plasma fractionated metanephrines A 63-year-old man is evaluated in the hospital for acute (D) Obtain renal artery imaging kidney injury following a motor vehicle accident 48 hours ago. He sustained pelvic and rib fractures and a splenic lac- eration requiring splenectomy. He received isotonic fluids Item 57 (17 L) plus norepinephrine for blood pressure support. He A 54-year-old woman is evaluated in the hospital for poly- is intubated and on mechanical ventilation. During the uria 3 days after undergoing resection of a glioblastoma past 24 hours, urine output fluctuated from 10 to 15 mL/h, multiforme. She is receiving 0.45% saline at 50 mL/h and with a 24-hour urine output of 280 mL. Medications are nasogastric enteral nutrition because of difficulty swallow- vancomycin, ceftazidime, intravenous norepinephrine, and ing. Medications are dexamethasone and levetiracetam. 150 mL/h of intravenous crystalloid fluids. On physical examination, she is in no acute distress. On physical examination, the patient is mechanically Vital signs are normal. Muscle strength is 4/5 in her left upper ventilated and sedated. Temperature is 38.3 °C (100.9 °F), extremity. The remainder of the examination is normal. blood pressure is 88/52 mm Hg, pulse rate is 96/min, and respiration rate is 16/min. Oxygen saturation is 95% with Laboratory studies: Blood urea nitrogen 85 mg/dL (30.3 mmol/L) the patient breathing 0.40 Fio,. Jugular venous pressure

Which of the following is the most appropriate next step in (B) Mycophenolate mofetil management? (C) Prednisone (D) Tacrolimus (A) Add chlorthalidone (B) Measure plasma aldosterone concentration/plasma renin activity ratio Item 59 (C) Measure plasma fractionated metanephrines A 63-year-old man is evaluated in the hospital for acute (D) Obtain renal artery imaging kidney injury following a motor vehicle accident 48 hours ago. He sustained pelvic and rib fractures and a splenic lac- eration requiring splenectomy. He received isotonic fluids Item 57 (17 L) plus norepinephrine for blood pressure support. He A 54-year-old woman is evaluated in the hospital for poly- is intubated and on mechanical ventilation. During the uria 3 days after undergoing resection of a glioblastoma past 24 hours, urine output fluctuated from 10 to 15 mL/h, multiforme. She is receiving 0.45% saline at 50 mL/h and with a 24-hour urine output of 280 mL. Medications are nasogastric enteral nutrition because of difficulty swallow- vancomycin, ceftazidime, intravenous norepinephrine, and ing. Medications are dexamethasone and levetiracetam. 150 mL/h of intravenous crystalloid fluids. On physical examination, she is in no acute distress. On physical examination, the patient is mechanically Vital signs are normal. Muscle strength is 4/5 in her left upper ventilated and sedated. Temperature is 38.3 °C (100.9 °F), extremity. The remainder of the examination is normal. blood pressure is 88/52 mm Hg, pulse rate is 96/min, and respiration rate is 16/min. Oxygen saturation is 95% with Laboratory studies: Blood urea nitrogen 85 mg/dL (30.3 mmol/L) the patient breathing 0.40 Fio,. Jugular venous pressure Creatinine 1.4 mg/dL (123.8 umol/L) is elevated. Cardiac examination is normal, and lungs are

Which of the following is the most appropriate next step in (B) Mycophenolate mofetil management? (C) Prednisone (D) Tacrolimus (A) Add chlorthalidone (B) Measure plasma aldosterone concentration/plasma renin activity ratio Item 59 (C) Measure plasma fractionated metanephrines A 63-year-old man is evaluated in the hospital for acute (D) Obtain renal artery imaging kidney injury following a motor vehicle accident 48 hours ago. He sustained pelvic and rib fractures and a splenic lac- eration requiring splenectomy. He received isotonic fluids Item 57 (17 L) plus norepinephrine for blood pressure support. He A 54-year-old woman is evaluated in the hospital for poly- is intubated and on mechanical ventilation. During the uria 3 days after undergoing resection of a glioblastoma past 24 hours, urine output fluctuated from 10 to 15 mL/h, multiforme. She is receiving 0.45% saline at 50 mL/h and with a 24-hour urine output of 280 mL. Medications are nasogastric enteral nutrition because of difficulty swallow- vancomycin, ceftazidime, intravenous norepinephrine, and ing. Medications are dexamethasone and levetiracetam. 150 mL/h of intravenous crystalloid fluids. On physical examination, she is in no acute distress. On physical examination, the patient is mechanically Vital signs are normal. Muscle strength is 4/5 in her left upper ventilated and sedated. Temperature is 38.3 °C (100.9 °F), extremity. The remainder of the examination is normal. blood pressure is 88/52 mm Hg, pulse rate is 96/min, and respiration rate is 16/min. Oxygen saturation is 95% with Laboratory studies: Blood urea nitrogen 85 mg/dL (30.3 mmol/L) the patient breathing 0.40 Fio,. Jugular venous pressure Creatinine 1.4 mg/dL (123.8 umol/L) is elevated. Cardiac examination is normal, and lungs are Electrolytes: clear to auscultation. The abdomen is distended and tense. A Sodium 152 mEq/L (152 mmol/L) bladder catheter is draining small amounts of urine.

Creatinine 1.4 mg/dL (123.8 umol/L) is elevated. Cardiac examination is normal, and lungs are Electrolytes: clear to auscultation. The abdomen is distended and tense. A Sodium 152 mEq/L (152 mmol/L) bladder catheter is draining small amounts of urine. Potassium 3.8 mEq/L (3.8 mmol/L) Laboratory studies: Chloride 118 mEq/L (118 mmol/L) Hemoglobin 8.5 g/dL (85 g/L) Bicarbonate 23 mEq/L (23 mmol/L) Blood urea nitrogen 73 mg/dL (26.1 mmol/L) Glucose 170 mg/dL (9.4 mmol/L) Creatinine 3.6 mg/dL (318.2 umol/L) Urine sodium 32 mEq/L (32 mmol/L) Urinalysis Specific gravity 1.012; pH 5.5; 1+ Urine potassium 24 mEq/L (24 mmol/L) blood; no protein; 1-3 erythrocytes/ Urine osmolality 560 mOsm/kg H,O hpf; scattered hyaline casts 108

pen mapeserean) Tse shed ~” a Which of the following is the most appropriate diagnostic Which of the following is the most appropriate additional = at test to perform next? treatment? = CONT. a (A) Bladder pressure measurement (A) Carvedilol Ee wn (B) CT urography (B) Furosemide wn w +) (C) Kidney biopsy (C) Hydralazine wn (D) Kidney ultrasonography (D) Lisinopril = = ) oa)

(D) Kidney ultrasonography (D) Lisinopril = = ) oa) Item 62 Item 60 A 36-year-old woman is evaluated during a routine follow- A 46-year-old man is evaluated in the hospital for hyperna- up visit for stage G4 chronic kidney disease. Her esti- tremia. He was hospitalized 2 days ago with hyperglycemic mated glomerular filtration rate is 22 mL/min/1.73 m?. hyperosmolar syndrome. He was obtunded and intubated Medications are lisinopril, sevelamer, and sodium bicarbon- to protect his airway. He was treated with 3 liters of 0.9% ate. She has selected hemodialysis for her renal replacement saline and insulin infusion. Medical history is significant for therapy, and an arteriovenous fistula will eventually be type 2 diabetes mellitus treated with metformin. placed in her nondominant left arm. On hospital day 2, blood pressure is 155/96 mm Hg, and Three weeks later, the patient is hospitalized with sep- pulse rate is 76/min. Other vital signs and the remainder of tic shock secondary to community-acquired pneumonia. the examination are normal. Venous access for the administration of fluids, vasopressors, The patient is extubated but his level of consciousness and antibiotics is urgently needed. fluctuates and he cannot follow commands or eat or drink fluids without choking. Which of the following is most appropriate method of Current laboratory studies: venous access for this patient? Electrolytes: (A) Internal jugular vein insertion of a central venous Sodium 152 mEq/L (152 mmol/L) catheter Potassium 3.2 mEq/L (3.2 mmol/L) (B) Peripherally inserted central catheter in the left arm Chloride 124 mEq/L (124 mmol/L) Bicarbonate 19 mEq/L (19 mmol/L) (C) Peripherally inserted central catheter in the right arm Glucose 200 mg/dL (11.1 mmol/L) (D) Subclavian vein insertion of a central venous catheter

Item 62 Item 60 A 36-year-old woman is evaluated during a routine follow- A 46-year-old man is evaluated in the hospital for hyperna- up visit for stage G4 chronic kidney disease. Her esti- tremia. He was hospitalized 2 days ago with hyperglycemic mated glomerular filtration rate is 22 mL/min/1.73 m?. hyperosmolar syndrome. He was obtunded and intubated Medications are lisinopril, sevelamer, and sodium bicarbon- to protect his airway. He was treated with 3 liters of 0.9% ate. She has selected hemodialysis for her renal replacement saline and insulin infusion. Medical history is significant for therapy, and an arteriovenous fistula will eventually be type 2 diabetes mellitus treated with metformin. placed in her nondominant left arm. On hospital day 2, blood pressure is 155/96 mm Hg, and Three weeks later, the patient is hospitalized with sep- pulse rate is 76/min. Other vital signs and the remainder of tic shock secondary to community-acquired pneumonia. the examination are normal. Venous access for the administration of fluids, vasopressors, The patient is extubated but his level of consciousness and antibiotics is urgently needed. fluctuates and he cannot follow commands or eat or drink fluids without choking. Which of the following is most appropriate method of Current laboratory studies: venous access for this patient? Electrolytes: (A) Internal jugular vein insertion of a central venous Sodium 152 mEq/L (152 mmol/L) catheter Potassium 3.2 mEq/L (3.2 mmol/L) (B) Peripherally inserted central catheter in the left arm Chloride 124 mEq/L (124 mmol/L) Bicarbonate 19 mEq/L (19 mmol/L) (C) Peripherally inserted central catheter in the right arm Glucose 200 mg/dL (11.1 mmol/L) (D) Subclavian vein insertion of a central venous catheter Which of the following is the most appropriate treatment for this patient’s hypernatremia? Item 63 A 25-year-old man is evaluated in the emergency department (A) Intravenous 5% dextrose for a 1-week history of fatigue, dyspnea, and hemoptysis. He (B) Intravenous 0.45% saline has no other medical problems and takes no medications. (C) Intravenous 0.9% saline On physical examination, blood pressure is 155/95 mm (D) Water via nasogastric tube Hg, and respiration rate is 25/min; other vital signs are nor- mal. No rash is noted. The remainder of the examination is unremarkable. Item 61 Laboratory studies:

Which of the following is the most appropriate treatment for this patient’s hypernatremia? Item 63 A 25-year-old man is evaluated in the emergency department (A) Intravenous 5% dextrose for a 1-week history of fatigue, dyspnea, and hemoptysis. He (B) Intravenous 0.45% saline has no other medical problems and takes no medications. (C) Intravenous 0.9% saline On physical examination, blood pressure is 155/95 mm (D) Water via nasogastric tube Hg, and respiration rate is 25/min; other vital signs are nor- mal. No rash is noted. The remainder of the examination is unremarkable. Item 61 Laboratory studies: A 62-year-old woman is evaluated during a follow-up visit C3 95 mg/dL (950 mg/L) for hypertension and chronic kidney disease. Medical his- C4 20 mg/dL (200 mg/L) tory is otherwise unremarkable. Medications are losartan Creatinine 2.3 mg/dL (203.3 umol/L) and amlodipine. The patient is adherent to her medication Antinuclear antibodies Negative regimen and low sodium diet. Antimyeloperoxidase Negative On physical examination, blood pressure is 148/94 mm antibodies Hg in both arms, pulse rate is 65/min, and respiration Antiproteinase-3 antibodies Negative rate is 18/min. BMI is 30. Neck examination shows jugu- Urinalysis 3+ blood; 3+ protein; lar venous distension. Cardiac examination reveals an S, numerous erythrocytes gallop. Lungs are clear to auscultation. There is 1+ pitting and erythrocyte casts

rate is 18/min. BMI is 30. Neck examination shows jugu- Urinalysis 3+ blood; 3+ protein; lar venous distension. Cardiac examination reveals an S, numerous erythrocytes gallop. Lungs are clear to auscultation. There is 1+ pitting and erythrocyte casts edema over the pretibial lower extremities and ankles Kidney biopsy shows necrotizing and crescentic glo- bilaterally. The remainder of the examination is unre- merulonephritis with linear staining for IgG on immuno- markable. fluorescence. Laboratory studies: Bicarbonate 22 mEq/L (22 mmol/L) Which of the following is the most appropriate serologic Creatinine 2.6 mg/dL (229.8 pmol/L) test to perform next? Potassium 4.9 mEq/L (4.9 mmol/L) (A) Anti-double-stranded DNA antibodies Sodium 136 mEq/L (136 mmol/L) (B) Anti-glomerular basement membrane antibodies Urine albumin-creatinine ratio 1500 mg/g Estimated glomerular filtration 24 mL/min/1.73 m? (C) Anti-phospholipase A2 receptor antibodies rate (D) Circulating IgA levels 109

SeliAssessment Test wn 2 = Item 64 (C) Poor solute intake a A 73-year-old man is evaluated during a follow- a up visit (D) Psychogenic polydipsia © for an unexplained worsening of chronic kidney wH disease. (E) Syndrome of inappropriate antidiuretic hormone 3 i) Recent laboratory studies showed a serum creatini of 2.4 mg/dL (212.2 mol/L); 9 months ago, serum ne level secretion creati- = -* nine was 1.1 mg/dL (97.2 umol/L). He has had two episodes ry of idiopathic acute pancreatitis in the past 3 years. Item 66 wn - The physical examination, including vital signs, is normal. A 25-year-old woman is evaluated in the emerge ncy department for weakness and muscle cramps Laboratory studies: . During the past 3 months, she had a weight loss Creatinine 2.4 mg/dL (212.2 umol/L) of 15 kg (33.1 Ib). She has no other medical problems and Electrolytes: takes no medications. Sodium 138 mEq/L (138 mmol/L) On physical examination, blood pressure is 124/72 Potassium 5.3 mEq/L mm (5.3 mmol/L) Hg, pulse rate is 100/min, and respiration Chloride rate is 18/min. 108 mEq/L (108 mmol/L) BMI is 36. Muscle strength is 4/5 in the upper Bicarbonate and lower 20 mEq/L (20 mmol/L) extremities. Other than weakness, the Urinalysis remainder of the Specific gravity 1.020; pH 5.0: neurologic examination is normal. no blood; 1+ protein; 1+ glucose; Laboratory studies: no leukocyte esterase; 0-2 erythrocytes/hpf; 3-5 leukocytes/ Creatinine 0.8 mg/dL (70.7 umol/L) Electrolytes: hpf; moderate granular casts Sodium 135 mEq/L (135 mmol/L) Kidney ultrasound shows a 12-cm right kidney Potassium and a 2.4 mEq/L (2.4 mmol/L) 13-cm left kidney with a mild increase in cortical echoge- Chloride 79 mEq/L (79 mmol/L) nicity. Bicarbonate 44 mEq/L (44 mmol/L) Kidney biopsy shows chronic tubulointerstitial Arterial blood gases: nephri- tis with dense lymphoplasmacytic infiltrates. pH 7.61 Pco, 45 mm Hg (6.0 kPa) Which of the following is the most likely diagnos Urine chloride is? 3 mEq/L (3 mmol/L)

SeliAssessment Test wn 2 = Item 64 (C) Poor solute intake a A 73-year-old man is evaluated during a follow- a up visit (D) Psychogenic polydipsia © for an unexplained worsening of chronic kidney wH disease. (E) Syndrome of inappropriate antidiuretic hormone 3 i) Recent laboratory studies showed a serum creatini of 2.4 mg/dL (212.2 mol/L); 9 months ago, serum ne level secretion creati- = -* nine was 1.1 mg/dL (97.2 umol/L). He has had two episodes ry of idiopathic acute pancreatitis in the past 3 years. Item 66 wn - The physical examination, including vital signs, is normal. A 25-year-old woman is evaluated in the emerge ncy department for weakness and muscle cramps Laboratory studies: . During the past 3 months, she had a weight loss Creatinine 2.4 mg/dL (212.2 umol/L) of 15 kg (33.1 Ib). She has no other medical problems and Electrolytes: takes no medications. Sodium 138 mEq/L (138 mmol/L) On physical examination, blood pressure is 124/72 Potassium 5.3 mEq/L mm (5.3 mmol/L) Hg, pulse rate is 100/min, and respiration Chloride rate is 18/min. 108 mEq/L (108 mmol/L) BMI is 36. Muscle strength is 4/5 in the upper Bicarbonate and lower 20 mEq/L (20 mmol/L) extremities. Other than weakness, the Urinalysis remainder of the Specific gravity 1.020; pH 5.0: neurologic examination is normal. no blood; 1+ protein; 1+ glucose; Laboratory studies: no leukocyte esterase; 0-2 erythrocytes/hpf; 3-5 leukocytes/ Creatinine 0.8 mg/dL (70.7 umol/L) Electrolytes: hpf; moderate granular casts Sodium 135 mEq/L (135 mmol/L) Kidney ultrasound shows a 12-cm right kidney Potassium and a 2.4 mEq/L (2.4 mmol/L) 13-cm left kidney with a mild increase in cortical echoge- Chloride 79 mEq/L (79 mmol/L) nicity. Bicarbonate 44 mEq/L (44 mmol/L) Kidney biopsy shows chronic tubulointerstitial Arterial blood gases: nephri- tis with dense lymphoplasmacytic infiltrates. pH 7.61 Pco, 45 mm Hg (6.0 kPa) Which of the following is the most likely diagnos Urine chloride is? 3 mEq/L (3 mmol/L) (A) IgG4-related disease Which of the following is the most likely diagnos is? (B) Sarcoidosis (A) Bartter syndrome (C) Systemic lupus erythematosus (B) Cushing syndrome (D) Tubulointerstitial nephritis with uveitis (C) Primary hyperaldosteronism (D) Surreptitious vomiting Item 65 A 65-year-old man is evaluated for a 7-week history of Item 67 Hi) increasing fatigue and poor appetite. Medical history is otherwise unremarkable. He takes no medicat A 37-year-old man is hospitalized for a ions. 2-month history Physical examination findings, including of anorexia, 4.5-kg (10-Ib) weight loss, vital signs, nocturia, morning are normal. nausea, and fatigue. He has no other medica l problems and takes no medications. Laboratory studies: Hematocrit On physical examination, blood pressure is 197/98 28% mm Hg, pulse rate is 80/min, and respiration Albumin 3.0 g/dL (30 g/L) rate is 18/min. BMI is 24, Funduscopic examination reveals Calcium 10.4 mg/dL (2.6 mmol/L) hypertensive retinopathy. There is no papilledema. Cardiac Creatinine 1.6 mg/dL (141.4 umol/L) examination reveals a sustained apical impulse and Electrolytes: an S,. The lungs are clear to auscultation. There is 1+ edema Sodium 130 mEq/L (130 mmol/L) of the lower extremities. Potassium 3.6 mEq/L (3.6 mmol/L) Chloride 99 mEq/L (99 mmol/L) Laboratory studies: Bicarbonate 23 mEq/L (23 mmol/L) Blood urea nitrogen 163 mg/dL (58.2 mmol/L) Osmolality 290 mOsm/kg HO Creatinine 14.2 mg/dL (1255.3 umol/L) Total protein 9.8 g/dL (98 g/L) Electrolytes: Urine osmolality 240 mOsm/kg H,O Sodium 134 mEq/L (134 mmol/L) Urine sodium 45 mEq/L (45 mmol/L) Potassium 4.9 mEq/L (4.9 mmol/L) Chloride 103 mEq/L (103 mmol/L) Which of the following is the most likely Bicarbonate cause of this 11 mEq/L (11 mmol/L) patient’s hyponatremia? Urinalysis Specific gravity 1.010; pH 7; 1+ (A) Hypercalcemia blood; 1+ protein; 2-5 erythrocytes/ hpf; 1-3 leukocytes/hpf:; scattered (B) Multiple myeloma granular and hyaline casts

(A) IgG4-related disease Which of the following is the most likely diagnos is? (B) Sarcoidosis (A) Bartter syndrome (C) Systemic lupus erythematosus (B) Cushing syndrome (D) Tubulointerstitial nephritis with uveitis (C) Primary hyperaldosteronism (D) Surreptitious vomiting Item 65 A 65-year-old man is evaluated for a 7-week history of Item 67 Hi) increasing fatigue and poor appetite. Medical history is otherwise unremarkable. He takes no medicat A 37-year-old man is hospitalized for a ions. 2-month history Physical examination findings, including of anorexia, 4.5-kg (10-Ib) weight loss, vital signs, nocturia, morning are normal. nausea, and fatigue. He has no other medica l problems and takes no medications. Laboratory studies: Hematocrit On physical examination, blood pressure is 197/98 28% mm Hg, pulse rate is 80/min, and respiration Albumin 3.0 g/dL (30 g/L) rate is 18/min. BMI is 24, Funduscopic examination reveals Calcium 10.4 mg/dL (2.6 mmol/L) hypertensive retinopathy. There is no papilledema. Cardiac Creatinine 1.6 mg/dL (141.4 umol/L) examination reveals a sustained apical impulse and Electrolytes: an S,. The lungs are clear to auscultation. There is 1+ edema Sodium 130 mEq/L (130 mmol/L) of the lower extremities. Potassium 3.6 mEq/L (3.6 mmol/L) Chloride 99 mEq/L (99 mmol/L) Laboratory studies: Bicarbonate 23 mEq/L (23 mmol/L) Blood urea nitrogen 163 mg/dL (58.2 mmol/L) Osmolality 290 mOsm/kg HO Creatinine 14.2 mg/dL (1255.3 umol/L) Total protein 9.8 g/dL (98 g/L) Electrolytes: Urine osmolality 240 mOsm/kg H,O Sodium 134 mEq/L (134 mmol/L) Urine sodium 45 mEq/L (45 mmol/L) Potassium 4.9 mEq/L (4.9 mmol/L) Chloride 103 mEq/L (103 mmol/L) Which of the following is the most likely Bicarbonate cause of this 11 mEq/L (11 mmol/L) patient’s hyponatremia? Urinalysis Specific gravity 1.010; pH 7; 1+ (A) Hypercalcemia blood; 1+ protein; 2-5 erythrocytes/ hpf; 1-3 leukocytes/hpf:; scattered (B) Multiple myeloma granular and hyaline casts 110

Ea Asagwamnent Test ‘oe? cH Kidney ultrasound shows a 7.3-cm right kidney and marrow biopsy, which confirmed the presence of acute _ sot a 7.7-cm left kidney; there is marked cortical echogenicity lymphoblastic leukemia. On admission, blood urea nitrogen a CONT. ct) and loss of corticomedullary distinction but no hydrone- level was 24 mg/dL (8.6 mmol/L) and serum creatinine level = phrosis. was 1.0 mg/dL (88.4 umol/L). Intravenous 0.9% saline was wn wn started at 125 mL/h. This morning, his serum creatinine level we wn Which of the following is the most appropriate is 1.9 mg/dL (168 umol/L). His urine output diminished to 7) management? less than 50 mL/h. = ail

a 7.7-cm left kidney; there is marked cortical echogenicity lymphoblastic leukemia. On admission, blood urea nitrogen a CONT. ct) and loss of corticomedullary distinction but no hydrone- level was 24 mg/dL (8.6 mmol/L) and serum creatinine level = phrosis. was 1.0 mg/dL (88.4 umol/L). Intravenous 0.9% saline was wn wn started at 125 mL/h. This morning, his serum creatinine level we wn Which of the following is the most appropriate is 1.9 mg/dL (168 umol/L). His urine output diminished to 7) management? less than 50 mL/h. = ail On physical examination, vital signs are normal. There oo a) (A) Dialysis are few scattered ecchymoses on the upper and lower (B) Intravenous 0.9% saline extremities. The remainder of the examination is normal. (C) Intravenous methylprednisolone Laboratory studies (hospital day 2): (D) Percutaneous kidney biopsy Blood urea 46 mg/dL (16.4 mmol/L) nitrogen Calcium 6.3 mg/dL (1.6 mmol/L) Item 68 Creatinine 1.9 mg/dL (168 umol/L) Electrolytes: A 52-year-old woman is evaluated during a follow-up visit Sodium 137 mEq/L (137 mmol/L) for hypertension. Losartan and chlorthalidone were started Potassium 6.1 mEq/L (6.1 mmol/L) 1 month ago. She adheres to her medication regimen and low Chloride 103 mEq/L (103 mmol/L) sodium diet. She has no other medical problems and takes no Bicarbonate 17 mEq/L (17 mmol/L) other medications. Previous ECG and results of a compre- Phosphorus 9.6 mg/dL (3.1 mmol/L) hensive metabolic profile and urinalysis were normal. Urate 15.2 mg/dL (0.90 mmol/L) On physical examination, blood pressure is 145/82 mm Urinalysis Specific gravity 1.010; pH 5.0; 1+ Hg, and pulse rate is 70/min; other vital signs are normal. blood; trace protein; multiple uric acid The remainder of the examination is unremarkable. crystals, scattered granular casts and Laboratory studies show a serum creatinine level of hyaline casts 0.8 mg/dL (70.7 umol/L) and a serum potassium level of 3.6 mEq/L (3.6 mmol/L). Intravenous 0.9% saline is increased to 200 mL/h.

On physical examination, vital signs are normal. There oo a) (A) Dialysis are few scattered ecchymoses on the upper and lower (B) Intravenous 0.9% saline extremities. The remainder of the examination is normal. (C) Intravenous methylprednisolone Laboratory studies (hospital day 2): (D) Percutaneous kidney biopsy Blood urea 46 mg/dL (16.4 mmol/L) nitrogen Calcium 6.3 mg/dL (1.6 mmol/L) Item 68 Creatinine 1.9 mg/dL (168 umol/L) Electrolytes: A 52-year-old woman is evaluated during a follow-up visit Sodium 137 mEq/L (137 mmol/L) for hypertension. Losartan and chlorthalidone were started Potassium 6.1 mEq/L (6.1 mmol/L) 1 month ago. She adheres to her medication regimen and low Chloride 103 mEq/L (103 mmol/L) sodium diet. She has no other medical problems and takes no Bicarbonate 17 mEq/L (17 mmol/L) other medications. Previous ECG and results of a compre- Phosphorus 9.6 mg/dL (3.1 mmol/L) hensive metabolic profile and urinalysis were normal. Urate 15.2 mg/dL (0.90 mmol/L) On physical examination, blood pressure is 145/82 mm Urinalysis Specific gravity 1.010; pH 5.0; 1+ Hg, and pulse rate is 70/min; other vital signs are normal. blood; trace protein; multiple uric acid The remainder of the examination is unremarkable. crystals, scattered granular casts and Laboratory studies show a serum creatinine level of hyaline casts 0.8 mg/dL (70.7 umol/L) and a serum potassium level of 3.6 mEq/L (3.6 mmol/L). Intravenous 0.9% saline is increased to 200 mL/h. Which of the following is the most appropriate additional Which of the following is the most appropriate additional treatment? treatment?

On physical examination, vital signs are normal. There oo a) (A) Dialysis are few scattered ecchymoses on the upper and lower (B) Intravenous 0.9% saline extremities. The remainder of the examination is normal. (C) Intravenous methylprednisolone Laboratory studies (hospital day 2): (D) Percutaneous kidney biopsy Blood urea 46 mg/dL (16.4 mmol/L) nitrogen Calcium 6.3 mg/dL (1.6 mmol/L) Item 68 Creatinine 1.9 mg/dL (168 umol/L) Electrolytes: A 52-year-old woman is evaluated during a follow-up visit Sodium 137 mEq/L (137 mmol/L) for hypertension. Losartan and chlorthalidone were started Potassium 6.1 mEq/L (6.1 mmol/L) 1 month ago. She adheres to her medication regimen and low Chloride 103 mEq/L (103 mmol/L) sodium diet. She has no other medical problems and takes no Bicarbonate 17 mEq/L (17 mmol/L) other medications. Previous ECG and results of a compre- Phosphorus 9.6 mg/dL (3.1 mmol/L) hensive metabolic profile and urinalysis were normal. Urate 15.2 mg/dL (0.90 mmol/L) On physical examination, blood pressure is 145/82 mm Urinalysis Specific gravity 1.010; pH 5.0; 1+ Hg, and pulse rate is 70/min; other vital signs are normal. blood; trace protein; multiple uric acid The remainder of the examination is unremarkable. crystals, scattered granular casts and Laboratory studies show a serum creatinine level of hyaline casts 0.8 mg/dL (70.7 umol/L) and a serum potassium level of 3.6 mEq/L (3.6 mmol/L). Intravenous 0.9% saline is increased to 200 mL/h. Which of the following is the most appropriate additional Which of the following is the most appropriate additional treatment? treatment? (A) Aliskiren (A) Allopurinol (B) Amlodipine (B) Febuxostat (C) Hydralazine (C) Rasburicase (D) Hydrochlorothiazide (D) Urinary alkalinization

(A) Aliskiren (A) Allopurinol (B) Amlodipine (B) Febuxostat (C) Hydralazine (C) Rasburicase (D) Hydrochlorothiazide (D) Urinary alkalinization Item 71 Item 69 A 24-year-old man is evaluated in the emergency depart- A 26-year-old woman is evaluated in the emergency depart- ment for a 3-hour history of right flank pain that radiates ment for acute flank pain and gross hematuria. to the groin. He reports nausea and dysuria but no fever On physical examination, the patient is afebrile. Pulse or chills. Medical history is otherwise unremarkable. He rate is 102/min; other vital signs are normal. Costovertebral takes no medications. Intravenous ketorolac is initiated angle tenderness is noted. The abdomen is soft and nontender. for pain. Urinalysis shows 3+ blood, trace protein, no nitrites or On physical examination, pulse rate is 104/min; other leukocyte esterase, 2-3 leukocytes/hpf, and too numerous vital signs are normal. The patient appears uncomfortable. to count erythrocytes. Pregnancy test is positive. Abdominal examination reveals right costovertebral ten- derness. The remainder of the examination is normal. Which of the following is the most appropriate diagnostic Laboratory studies show a serum calcium level of test to perform next? 9.8 mg/dL (2.5 mmol/L) and a serum creatinine level of (A) Abdominal MRI 0.8 mg/dL (70.7 umol/L). Urinalysis shows a specific gravity (B) Kidney ultrasonography of 1.020; a pH of 5.0; 1+ blood; no leukocyte esterase; no nitrites; 20-30 erythrocytes/hpf; and 0-1 leukocytes/hpf. (C) Kidney, ureter, and bladder plain radiography (D) g Noncontrast helical abdominal CT Which of the following is the most sensitive imaging test to (E) Ureteroscopy perform?

Item 71 Item 69 A 24-year-old man is evaluated in the emergency depart- A 26-year-old woman is evaluated in the emergency depart- ment for a 3-hour history of right flank pain that radiates ment for acute flank pain and gross hematuria. to the groin. He reports nausea and dysuria but no fever On physical examination, the patient is afebrile. Pulse or chills. Medical history is otherwise unremarkable. He rate is 102/min; other vital signs are normal. Costovertebral takes no medications. Intravenous ketorolac is initiated angle tenderness is noted. The abdomen is soft and nontender. for pain. Urinalysis shows 3+ blood, trace protein, no nitrites or On physical examination, pulse rate is 104/min; other leukocyte esterase, 2-3 leukocytes/hpf, and too numerous vital signs are normal. The patient appears uncomfortable. to count erythrocytes. Pregnancy test is positive. Abdominal examination reveals right costovertebral ten- derness. The remainder of the examination is normal. Which of the following is the most appropriate diagnostic Laboratory studies show a serum calcium level of test to perform next? 9.8 mg/dL (2.5 mmol/L) and a serum creatinine level of (A) Abdominal MRI 0.8 mg/dL (70.7 umol/L). Urinalysis shows a specific gravity (B) Kidney ultrasonography of 1.020; a pH of 5.0; 1+ blood; no leukocyte esterase; no nitrites; 20-30 erythrocytes/hpf; and 0-1 leukocytes/hpf. (C) Kidney, ureter, and bladder plain radiography (D) g Noncontrast helical abdominal CT Which of the following is the most sensitive imaging test to (E) Ureteroscopy perform? (A) Intravenous pyelography

Item 71 Item 69 A 24-year-old man is evaluated in the emergency depart- A 26-year-old woman is evaluated in the emergency depart- ment for a 3-hour history of right flank pain that radiates ment for acute flank pain and gross hematuria. to the groin. He reports nausea and dysuria but no fever On physical examination, the patient is afebrile. Pulse or chills. Medical history is otherwise unremarkable. He rate is 102/min; other vital signs are normal. Costovertebral takes no medications. Intravenous ketorolac is initiated angle tenderness is noted. The abdomen is soft and nontender. for pain. Urinalysis shows 3+ blood, trace protein, no nitrites or On physical examination, pulse rate is 104/min; other leukocyte esterase, 2-3 leukocytes/hpf, and too numerous vital signs are normal. The patient appears uncomfortable. to count erythrocytes. Pregnancy test is positive. Abdominal examination reveals right costovertebral ten- derness. The remainder of the examination is normal. Which of the following is the most appropriate diagnostic Laboratory studies show a serum calcium level of test to perform next? 9.8 mg/dL (2.5 mmol/L) and a serum creatinine level of (A) Abdominal MRI 0.8 mg/dL (70.7 umol/L). Urinalysis shows a specific gravity (B) Kidney ultrasonography of 1.020; a pH of 5.0; 1+ blood; no leukocyte esterase; no nitrites; 20-30 erythrocytes/hpf; and 0-1 leukocytes/hpf. (C) Kidney, ureter, and bladder plain radiography (D) g Noncontrast helical abdominal CT Which of the following is the most sensitive imaging test to (E) Ureteroscopy perform? (A) Intravenous pyelography Item 70 (B) Kidney and bladder ultrasonography

Item 71 Item 69 A 24-year-old man is evaluated in the emergency depart- A 26-year-old woman is evaluated in the emergency depart- ment for a 3-hour history of right flank pain that radiates ment for acute flank pain and gross hematuria. to the groin. He reports nausea and dysuria but no fever On physical examination, the patient is afebrile. Pulse or chills. Medical history is otherwise unremarkable. He rate is 102/min; other vital signs are normal. Costovertebral takes no medications. Intravenous ketorolac is initiated angle tenderness is noted. The abdomen is soft and nontender. for pain. Urinalysis shows 3+ blood, trace protein, no nitrites or On physical examination, pulse rate is 104/min; other leukocyte esterase, 2-3 leukocytes/hpf, and too numerous vital signs are normal. The patient appears uncomfortable. to count erythrocytes. Pregnancy test is positive. Abdominal examination reveals right costovertebral ten- derness. The remainder of the examination is normal. Which of the following is the most appropriate diagnostic Laboratory studies show a serum calcium level of test to perform next? 9.8 mg/dL (2.5 mmol/L) and a serum creatinine level of (A) Abdominal MRI 0.8 mg/dL (70.7 umol/L). Urinalysis shows a specific gravity (B) Kidney ultrasonography of 1.020; a pH of 5.0; 1+ blood; no leukocyte esterase; no nitrites; 20-30 erythrocytes/hpf; and 0-1 leukocytes/hpf. (C) Kidney, ureter, and bladder plain radiography (D) g Noncontrast helical abdominal CT Which of the following is the most sensitive imaging test to (E) Ureteroscopy perform? (A) Intravenous pyelography Item 70 (B) Kidney and bladder ultrasonography A 17-year-old boy is evaluated in the hospital for acute (C) Kidney, ureter, and bladder radiography kidney injury. He was hospitalized 24 hours ago for a bone (D) Noncontrast helical abdomen and pelvis CT

Item 70 (B) Kidney and bladder ultrasonography A 17-year-old boy is evaluated in the hospital for acute (C) Kidney, ureter, and bladder radiography kidney injury. He was hospitalized 24 hours ago for a bone (D) Noncontrast helical abdomen and pelvis CT 111

Se 74) 2. = Item 72 Hg. Therapeutic lifestyle interventions and pharmacologic = therapies were initiated. Medical history is also significant 72) wn A 65-year-old man is evaluated during a follow-up visit for for peripheral vascular disease, hyperlipidemia, and type 2 © stage G4 chronic kidney disease. He has a reduced appe- wn diabetes mellitus. Other medications are glipizide, rosuvas- 3 @ tite but no other significant symptoms. Four months ago, anemia was discovered and confirmed to be related to his tatin, and low-dose aspirin. She lives independently in her = own home. rs chronic kidney disease. Medical history is also significant On physical examination, blood pressure is 144/69 mm for hypertension and type 2 diabetes mellitus. Medications o Hg, and pulse rate is 86/min. Cardiovascular examination n ~*~ are atenolol, atorvastatin, basal insulin, prandial insu- reveals an S, and diminished lower extremity pulses. There lin, metolazone, sevelamer, furosemide, hydralazine, and is no peripheral edema. The remainder of the examination nifedipine. is normal. On physical examination, vital signs are normal. There isa mature arteriovenous fistula with a thrill. The remainder Laboratory studies: of the examination is normal. Creatinine 1.4 mg/dL (123.8 pmol/L) Laboratory studies: Potassium 4.4 mEq/L (4.4 mmol/L) Estimated glomerular filtration 34 mL/min/1.73 m? Hemoglobin 10.1 g/dL (101 g/L) rate Creatinine 3.3 mg/dL (291.7 umol/L) Urine albumin-creatinine ratio 15 mg/g Potassium 4.2 mEq/L (4.2 mmol/L) Bicarbonate 19 mEq/L (19 mmol/L) Which of the following is the most appropriate Estimated glomerular 20 mL/min/1.73 m? management? filtration rate (A) Add chlorthalidone Which of the following is the most appropriate (B) Add prazosin treatment? (C) Switch lisinopril to ramipril (A) Erythropoietin-stimulating agent (D) Continue current medical therapy (B) Hemodialysis (C) High-protein diet Item 75 (D) Sodium bicarbonate supplement A 48-year-old man is evaluated in the emergency depart- ment for sudden onset of dyspnea. He has a 2-week history of progressive leg edema and bilateral flank Item 73 pain. He has no other medical problems and takes no A 35-year-old woman is evaluated during a follow-up visit medications. for recurrent microscopic hematuria without proteinuria. On physical examination, respiratory rate is 26/min; Family history is significant for microscopic hematuria in other vital signs are normal. There is 2-mm pitting edema her brother and mother; her two other siblings have no in the lower extremities to the mid-shin bilaterally. The urinary abnormalities. There is no family history of chronic remainder of the examination is unremarkable. kidney disease or end-stage kidney disease. Her medical Laboratory studies: history is otherwise unremarkable, and she takes no med- Albumin 2.0 g/dL (20 g/L) ications. Total cholesterol 401 mg/dL (10.4 mmol/L) Physical examination findings, including vital signs, Complement levels Normal are normal. Creatinine 1.1 mg/dL (97.2 umol/L) Laboratory studies show a serum creatinine level of Antinuclear antibodies Negative 0.7 mg/dL (61.9 umol/L); urinalysis shows 2+ blood, no Urinalysis No blood; 4+ protein; 0-1 protein, and 20-30 erythrocytes/hpf. erythrocytes/hpf; 0-1 Kidney ultrasound shows normal-sized kidneys with leukocytes/hpf no masses or stones. Urine protein-creatinine ratio 8900 mg/g

Se 74) 2. = Item 72 Hg. Therapeutic lifestyle interventions and pharmacologic = therapies were initiated. Medical history is also significant 72) wn A 65-year-old man is evaluated during a follow-up visit for for peripheral vascular disease, hyperlipidemia, and type 2 © stage G4 chronic kidney disease. He has a reduced appe- wn diabetes mellitus. Other medications are glipizide, rosuvas- 3 @ tite but no other significant symptoms. Four months ago, anemia was discovered and confirmed to be related to his tatin, and low-dose aspirin. She lives independently in her = own home. rs chronic kidney disease. Medical history is also significant On physical examination, blood pressure is 144/69 mm for hypertension and type 2 diabetes mellitus. Medications o Hg, and pulse rate is 86/min. Cardiovascular examination n ~*~ are atenolol, atorvastatin, basal insulin, prandial insu- reveals an S, and diminished lower extremity pulses. There lin, metolazone, sevelamer, furosemide, hydralazine, and is no peripheral edema. The remainder of the examination nifedipine. is normal. On physical examination, vital signs are normal. There isa mature arteriovenous fistula with a thrill. The remainder Laboratory studies: of the examination is normal. Creatinine 1.4 mg/dL (123.8 pmol/L) Laboratory studies: Potassium 4.4 mEq/L (4.4 mmol/L) Estimated glomerular filtration 34 mL/min/1.73 m? Hemoglobin 10.1 g/dL (101 g/L) rate Creatinine 3.3 mg/dL (291.7 umol/L) Urine albumin-creatinine ratio 15 mg/g Potassium 4.2 mEq/L (4.2 mmol/L) Bicarbonate 19 mEq/L (19 mmol/L) Which of the following is the most appropriate Estimated glomerular 20 mL/min/1.73 m? management? filtration rate (A) Add chlorthalidone Which of the following is the most appropriate (B) Add prazosin treatment? (C) Switch lisinopril to ramipril (A) Erythropoietin-stimulating agent (D) Continue current medical therapy (B) Hemodialysis (C) High-protein diet Item 75 (D) Sodium bicarbonate supplement A 48-year-old man is evaluated in the emergency depart- ment for sudden onset of dyspnea. He has a 2-week history of progressive leg edema and bilateral flank Item 73 pain. He has no other medical problems and takes no A 35-year-old woman is evaluated during a follow-up visit medications. for recurrent microscopic hematuria without proteinuria. On physical examination, respiratory rate is 26/min; Family history is significant for microscopic hematuria in other vital signs are normal. There is 2-mm pitting edema her brother and mother; her two other siblings have no in the lower extremities to the mid-shin bilaterally. The urinary abnormalities. There is no family history of chronic remainder of the examination is unremarkable. kidney disease or end-stage kidney disease. Her medical Laboratory studies: history is otherwise unremarkable, and she takes no med- Albumin 2.0 g/dL (20 g/L) ications. Total cholesterol 401 mg/dL (10.4 mmol/L) Physical examination findings, including vital signs, Complement levels Normal are normal. Creatinine 1.1 mg/dL (97.2 umol/L) Laboratory studies show a serum creatinine level of Antinuclear antibodies Negative 0.7 mg/dL (61.9 umol/L); urinalysis shows 2+ blood, no Urinalysis No blood; 4+ protein; 0-1 protein, and 20-30 erythrocytes/hpf. erythrocytes/hpf; 0-1 Kidney ultrasound shows normal-sized kidneys with leukocytes/hpf no masses or stones. Urine protein-creatinine ratio 8900 mg/g Hepatitis B and C, HIV, and syphilis testing results are Which of the following is the most likely diagnosis? negative. (A) Autosomal dominant tubulointerstitial kidney CT of the chest shows segmental pulmonary embolism. disease CT of the abdomen and pelvis shows bilateral renal vein

Hepatitis B and C, HIV, and syphilis testing results are Which of the following is the most likely diagnosis? negative. (A) Autosomal dominant tubulointerstitial kidney CT of the chest shows segmental pulmonary embolism. disease CT of the abdomen and pelvis shows bilateral renal vein (B) Fabry disease thromboses. Low-molecular-weight heparin is initiated. (C) Hereditary nephritis (Alport syndrome) (D) Thin glomerular basement membrane disease Which of the following is the most appropriate diagnostic test to perform next? Item 74 (A) ANCA antibodies (B) Anti-double-stranded DNA antibodies A 70-year-old woman is evaluated during a follow-up visit. One month ago, lisinopril was initiated for confirmed (C) Anti-phospholipase A2 receptor antibodies hypertension. Pretreatment blood pressure was 152/78 mm (D) Kidney biopsy following discontinuation of heparin 112

Self-Assessment Test Coal od Item 76 Item 78 i aot — A 58-year-old woman is evaluated during a follow-up visit A 28-year-old woman is evaluated for leg weakness and a for progressive stage G3 chronic kidney disease. Her average mild nausea several days after treatment with intravenous = n blood pressure using home blood pressure monitoring is ferric carboxymaltose for severe iron deficiency anemia. rn a 130/70 mm Hg. She walks three times weekly for exercise. She has Crohn disease. She reports that her appetite is good. wn w Medical history is also significant for hypertension. Medica- Medications are prednisone, sulfasalazine, infliximab, cal- = tions are chlorthalidone, cholecalciferol, furosemide, losar- cium carbonate, and vitamin D. = wD tan, and metoprolol. On physical examination, temperature is 37.0 °C 17) On physical examination, vital signs are normal. There (98.6 °F), pulse rate is 80/min, and respiration rate is is no jugular venous distension. Lungs are clear to ausculta- 16/min. BMI is 18. Abdominal examination reveals tender- tion. There is trace bilateral leg edema. ness. Motor strength is 4/5 in the hip flexors and extensors. The remainder of the examination is normal. Laboratory studies: Total cholesterol 178 mg/dL (4.61 mmol/L) Laboratory studies: Creatinine 1.5 mg/dL (132.6 umol/L) Electrolytes: Estimated glomerular filtration 44 mL/min/1.73 m? Sodium 136 mEq/L (136 mmol/L) rate Potassium 3.8 mEq/L (3.8 mmol/L) Urine albumin-creatinine ratio 420 mg/g Chloride 108 mEq/L (108 mmol/L) Bicarbonate 21 mEq/L (21 mmol/L) Which of the following is the most likely expected cause of Phosphorus 1.2 mg/dL (0.39 mmol/L) premature death in this patient? Fractional excretion of 21% phosphorus (A) Cardiovascular disease (B) End-stage kidney disease Which of the following is the most likely cause of this (C) Infection patient’s hypophosphatemia? (D) Renal cell carcinoma (A) Ferric carboxymaltose (B) Low phosphorus diet Item 77 (C) Metabolic acidosis A 62-year-old man is evaluated in the emergency (D) Prednisone department for increasing abdominal and bilateral flank pain. The pain began yesterday, 2 days after he took primaquine prescribed as antimalarial prophylaxis for Item 79 planned travel. A 67-year-old man is evaluated during a follow-up visit On physical examination, temperature is 38.1 °C for resistant hypertension. He was recently evaluated for (100.6 °F), blood pressure is 102/55 mm Hg, pulse rate is primary hyperaldosteronism, and the screening plasma 110/min, and respiration rate is 22/min. Cardiac exam- aldosterone concentration/plasma renin activity ratio was ination reveals tachycardia without extra sounds. There >20. A dedicated adrenal CT scan showed diffuse bilateral is no edema. The remainder of the examination is unre- adrenal hyperplasia. The patient also has type 2 diabetes markable. mellitus, hyperlipidemia, coronary artery disease, and Laboratory studies: activity-limiting COPD. He does not want surgery under Haptoglobin 10 mg/dL (100 mg/L) any circumstances. Medications are rosuvastatin, met- Hemoglobin 7.9 g/dL (79 g/L) formin, canagliflozin, amlodipine, enalapril, metoprolol, Reticulocyte count 8% chlorthalidone, low-dose aspirin, albuterol, and tiotropium. Total bilirubin 5.8 mg/dL (99.2 umol/L) On physical examination, blood pressure is 160/94 mm Blood urea nitrogen 32 mg/dL (11.4 mmol/L) Hg in both arms, pulse rate is 76/min, and respiration rate Creatinine 1.9 mg/dL (168 nmol/L) is 18/min. BMI is 24. Cardiac examination is notable for an Lactate dehydrogenase 1250 U/L S,. Pulmonary examination reveals occasional expiratory Urinalysis Specific gravity 1.010; pH wheezing. 5.0; 3+ heme; 1+ albumin; no erythrocytes, leukocytes, or Which of the following is the most appropriate next step in leukocyte esterase; numerous management? pigmented granular casts (A) Bilateral adrenal vein sampling Examination of peripheral blood smear shows bite (B) Eplerenone therapy cells. (C) MRI of the adrenal glands Which of the following is the most likely diagnosis? (D) Oral sodium loading test

— A 58-year-old woman is evaluated during a follow-up visit A 28-year-old woman is evaluated for leg weakness and a for progressive stage G3 chronic kidney disease. Her average mild nausea several days after treatment with intravenous = n blood pressure using home blood pressure monitoring is ferric carboxymaltose for severe iron deficiency anemia. rn a 130/70 mm Hg. She walks three times weekly for exercise. She has Crohn disease. She reports that her appetite is good. wn w Medical history is also significant for hypertension. Medica- Medications are prednisone, sulfasalazine, infliximab, cal- = tions are chlorthalidone, cholecalciferol, furosemide, losar- cium carbonate, and vitamin D. = wD tan, and metoprolol. On physical examination, temperature is 37.0 °C 17) On physical examination, vital signs are normal. There (98.6 °F), pulse rate is 80/min, and respiration rate is is no jugular venous distension. Lungs are clear to ausculta- 16/min. BMI is 18. Abdominal examination reveals tender- tion. There is trace bilateral leg edema. ness. Motor strength is 4/5 in the hip flexors and extensors. The remainder of the examination is normal. Laboratory studies: Total cholesterol 178 mg/dL (4.61 mmol/L) Laboratory studies: Creatinine 1.5 mg/dL (132.6 umol/L) Electrolytes: Estimated glomerular filtration 44 mL/min/1.73 m? Sodium 136 mEq/L (136 mmol/L) rate Potassium 3.8 mEq/L (3.8 mmol/L) Urine albumin-creatinine ratio 420 mg/g Chloride 108 mEq/L (108 mmol/L) Bicarbonate 21 mEq/L (21 mmol/L) Which of the following is the most likely expected cause of Phosphorus 1.2 mg/dL (0.39 mmol/L) premature death in this patient? Fractional excretion of 21% phosphorus (A) Cardiovascular disease (B) End-stage kidney disease Which of the following is the most likely cause of this (C) Infection patient’s hypophosphatemia? (D) Renal cell carcinoma (A) Ferric carboxymaltose (B) Low phosphorus diet Item 77 (C) Metabolic acidosis A 62-year-old man is evaluated in the emergency (D) Prednisone department for increasing abdominal and bilateral flank pain. The pain began yesterday, 2 days after he took primaquine prescribed as antimalarial prophylaxis for Item 79 planned travel. A 67-year-old man is evaluated during a follow-up visit On physical examination, temperature is 38.1 °C for resistant hypertension. He was recently evaluated for (100.6 °F), blood pressure is 102/55 mm Hg, pulse rate is primary hyperaldosteronism, and the screening plasma 110/min, and respiration rate is 22/min. Cardiac exam- aldosterone concentration/plasma renin activity ratio was ination reveals tachycardia without extra sounds. There >20. A dedicated adrenal CT scan showed diffuse bilateral is no edema. The remainder of the examination is unre- adrenal hyperplasia. The patient also has type 2 diabetes markable. mellitus, hyperlipidemia, coronary artery disease, and Laboratory studies: activity-limiting COPD. He does not want surgery under Haptoglobin 10 mg/dL (100 mg/L) any circumstances. Medications are rosuvastatin, met- Hemoglobin 7.9 g/dL (79 g/L) formin, canagliflozin, amlodipine, enalapril, metoprolol, Reticulocyte count 8% chlorthalidone, low-dose aspirin, albuterol, and tiotropium. Total bilirubin 5.8 mg/dL (99.2 umol/L) On physical examination, blood pressure is 160/94 mm Blood urea nitrogen 32 mg/dL (11.4 mmol/L) Hg in both arms, pulse rate is 76/min, and respiration rate Creatinine 1.9 mg/dL (168 nmol/L) is 18/min. BMI is 24. Cardiac examination is notable for an Lactate dehydrogenase 1250 U/L S,. Pulmonary examination reveals occasional expiratory Urinalysis Specific gravity 1.010; pH wheezing. 5.0; 3+ heme; 1+ albumin; no erythrocytes, leukocytes, or Which of the following is the most appropriate next step in leukocyte esterase; numerous management? pigmented granular casts (A) Bilateral adrenal vein sampling Examination of peripheral blood smear shows bite (B) Eplerenone therapy cells. (C) MRI of the adrenal glands Which of the following is the most likely diagnosis? (D) Oral sodium loading test (A) Acute interstitial nephritis (B) Heme pigment nephropathy Item 80 (C) Prerenal acute kidney injury A 45-year-old woman is evaluated in the emergency depart (D) Rhabdomyolysis ment for altered mental status.

Self-Assessment Test nn © — On physical examination, the patient is tachypneic and Which of the following viral studies will support the most > obtunded. Temperature is normal, blood pressure is 94/64 mm wn likely diagnosis? wn CONT. Hg, pulse rate is 80/min, and respiration rate is 24/min. @ wn (A) Fourth-generation HIV testing wn Laboratory studies: =] (B) Hepatitis A virus antibody testing Electrolytes: @ s Sodium 133 mEq/L (133 mmol/L) (C) Hepatitis B virus surface antigen and surface antibody - testing Potassium 3.9 mEq/L (3.9 mmol/L) o wn ov Chloride 110 mEq/L (110 mmol/L) (D) Hepatitis C virus antibody testing Bicarbonate 16 mEq/L (16 mmol/L) Arterial blood gases: Item 82 pH 7.4 Pco, 27 mm Hg (3.6 kPa) A 57-year-old man is evaluated during a follow-up visit after beginning hydrochlorothiazide 1 month ago. He has hyper- Which of the following is the most likely acid-base disorder? tension and chronic kidney disease. He has no other medi- cal problems. Medications are lisinopril, 40 mg once daily; (A) Respiratory alkalosis and increased anion gap meta- amlodipine, 10 mg once daily; and hydrochlorothiazide, bolic acidosis 25 mg once daily. The patient maintains a low sodium diet. (B) Respiratory alkalosis and normal anion gap metabolic On physical examination, blood pressure is 138/86 mm acidosis Hg; other vital signs are normal. There is 1+ pitting pretib- (C) Respiratory alkalosis, normal gap metabolic acidosis, ial edema bilaterally. The remainder of the examination is and metabolic alkalosis normal. (D) Respiratory alkalosis with chronic compensation Laboratory studies: Bicarbonate 22 mEq/L (22 mmol/L) Creatinine 2.5 mg/dL (221 umol/L) Item 81 Potassium 5.4 mEq/L (5.4 mmol/L) A 31-year-old woman is evaluated for lower extremity Sodium 135 mEq/L (135 mmol/L) edema, a rash over both legs, and fatigue that have wors- Estimated glomerular filtration 28 mL/min/1.73 m? ened during the past 3 months. She has no other medical rate problems and takes no medications. The patient was born Urine protein-creatinine ratio 1800 mg/g in Egypt and moved to the United States at 20 years of age. On physical examination, the patient is afebrile, and Which of the following is the most appropriate treatment? blood pressure is 147/96 mm Hg. There is 1-mm pitting (A) Discontinue hydrochlorothiazide; begin eplerenone edema through the mid-shins bilaterally. (B) Discontinue hydrochlorothiazide; begin furosemide The rash is shown. (C) Increase hydrochlorothiazide dose (D) Continue current management

nn © — On physical examination, the patient is tachypneic and Which of the following viral studies will support the most > obtunded. Temperature is normal, blood pressure is 94/64 mm wn likely diagnosis? wn CONT. Hg, pulse rate is 80/min, and respiration rate is 24/min. @ wn (A) Fourth-generation HIV testing wn Laboratory studies: =] (B) Hepatitis A virus antibody testing Electrolytes: @ s Sodium 133 mEq/L (133 mmol/L) (C) Hepatitis B virus surface antigen and surface antibody - testing Potassium 3.9 mEq/L (3.9 mmol/L) o wn ov Chloride 110 mEq/L (110 mmol/L) (D) Hepatitis C virus antibody testing Bicarbonate 16 mEq/L (16 mmol/L) Arterial blood gases: Item 82 pH 7.4 Pco, 27 mm Hg (3.6 kPa) A 57-year-old man is evaluated during a follow-up visit after beginning hydrochlorothiazide 1 month ago. He has hyper- Which of the following is the most likely acid-base disorder? tension and chronic kidney disease. He has no other medi- cal problems. Medications are lisinopril, 40 mg once daily; (A) Respiratory alkalosis and increased anion gap meta- amlodipine, 10 mg once daily; and hydrochlorothiazide, bolic acidosis 25 mg once daily. The patient maintains a low sodium diet. (B) Respiratory alkalosis and normal anion gap metabolic On physical examination, blood pressure is 138/86 mm acidosis Hg; other vital signs are normal. There is 1+ pitting pretib- (C) Respiratory alkalosis, normal gap metabolic acidosis, ial edema bilaterally. The remainder of the examination is and metabolic alkalosis normal. (D) Respiratory alkalosis with chronic compensation Laboratory studies: Bicarbonate 22 mEq/L (22 mmol/L) Creatinine 2.5 mg/dL (221 umol/L) Item 81 Potassium 5.4 mEq/L (5.4 mmol/L) A 31-year-old woman is evaluated for lower extremity Sodium 135 mEq/L (135 mmol/L) edema, a rash over both legs, and fatigue that have wors- Estimated glomerular filtration 28 mL/min/1.73 m? ened during the past 3 months. She has no other medical rate problems and takes no medications. The patient was born Urine protein-creatinine ratio 1800 mg/g in Egypt and moved to the United States at 20 years of age. On physical examination, the patient is afebrile, and Which of the following is the most appropriate treatment? blood pressure is 147/96 mm Hg. There is 1-mm pitting (A) Discontinue hydrochlorothiazide; begin eplerenone edema through the mid-shins bilaterally. (B) Discontinue hydrochlorothiazide; begin furosemide The rash is shown. (C) Increase hydrochlorothiazide dose (D) Continue current management Item 83

nn © — On physical examination, the patient is tachypneic and Which of the following viral studies will support the most > obtunded. Temperature is normal, blood pressure is 94/64 mm wn likely diagnosis? wn CONT. Hg, pulse rate is 80/min, and respiration rate is 24/min. @ wn (A) Fourth-generation HIV testing wn Laboratory studies: =] (B) Hepatitis A virus antibody testing Electrolytes: @ s Sodium 133 mEq/L (133 mmol/L) (C) Hepatitis B virus surface antigen and surface antibody - testing Potassium 3.9 mEq/L (3.9 mmol/L) o wn ov Chloride 110 mEq/L (110 mmol/L) (D) Hepatitis C virus antibody testing Bicarbonate 16 mEq/L (16 mmol/L) Arterial blood gases: Item 82 pH 7.4 Pco, 27 mm Hg (3.6 kPa) A 57-year-old man is evaluated during a follow-up visit after beginning hydrochlorothiazide 1 month ago. He has hyper- Which of the following is the most likely acid-base disorder? tension and chronic kidney disease. He has no other medi- cal problems. Medications are lisinopril, 40 mg once daily; (A) Respiratory alkalosis and increased anion gap meta- amlodipine, 10 mg once daily; and hydrochlorothiazide, bolic acidosis 25 mg once daily. The patient maintains a low sodium diet. (B) Respiratory alkalosis and normal anion gap metabolic On physical examination, blood pressure is 138/86 mm acidosis Hg; other vital signs are normal. There is 1+ pitting pretib- (C) Respiratory alkalosis, normal gap metabolic acidosis, ial edema bilaterally. The remainder of the examination is and metabolic alkalosis normal. (D) Respiratory alkalosis with chronic compensation Laboratory studies: Bicarbonate 22 mEq/L (22 mmol/L) Creatinine 2.5 mg/dL (221 umol/L) Item 81 Potassium 5.4 mEq/L (5.4 mmol/L) A 31-year-old woman is evaluated for lower extremity Sodium 135 mEq/L (135 mmol/L) edema, a rash over both legs, and fatigue that have wors- Estimated glomerular filtration 28 mL/min/1.73 m? ened during the past 3 months. She has no other medical rate problems and takes no medications. The patient was born Urine protein-creatinine ratio 1800 mg/g in Egypt and moved to the United States at 20 years of age. On physical examination, the patient is afebrile, and Which of the following is the most appropriate treatment? blood pressure is 147/96 mm Hg. There is 1-mm pitting (A) Discontinue hydrochlorothiazide; begin eplerenone edema through the mid-shins bilaterally. (B) Discontinue hydrochlorothiazide; begin furosemide The rash is shown. (C) Increase hydrochlorothiazide dose (D) Continue current management Item 83 A 59-year-old man is evaluated for recently discovered nor- mochromic, normocytic anemia and an elevated serum cre- atinine level. He is otherwise well and takes no medications. All physical examination findings, including vital signs and neurologic examination, are normal.

A 59-year-old man is evaluated for recently discovered nor- mochromic, normocytic anemia and an elevated serum cre- atinine level. He is otherwise well and takes no medications. All physical examination findings, including vital signs and neurologic examination, are normal. Laboratory studies: Hemoglobin 9.2 g/dL (92 g/L) Creatinine 3.0 mg/dL (265.2 umol/L); 1 year ago: 1.0 mg/dL (88.4 umol/L) Urinalysis Trace protein; no blood, erythrocytes, leukocytes, leukocyte esterase, or Laboratory studies: nitrites Albumin 3.9 g/dL (39 g/L) Urine protein- 2500 mg/g C3 58 mg/dL (580 mg/L) creatinine ratio C4 5.0 mg/dL (50 mg/L) Creatinine 2.6 mg/dL (229.8 umol/L) Which of the following is the most appropriate test to Cryoglobulins Positive perform next? Rheumatoid factor Positive Urinalysis 3+ blood; 3+ protein; ( A) Repeat urinalysis erythrocytes and rare (B) 24-Hour urine collection for total protein erythrocyte casts (C) Sulfosalicylic acid test Urine protein-creatinine ratio 2100 mg/g (D) Urine albumin-creatinine ratio A kidney biopsy is scheduled. (E) Urine protein electrophoresis

Laboratory studies: Hemoglobin 9.2 g/dL (92 g/L) Creatinine 3.0 mg/dL (265.2 umol/L); 1 year ago: 1.0 mg/dL (88.4 umol/L) Urinalysis Trace protein; no blood, erythrocytes, leukocytes, leukocyte esterase, or Laboratory studies: nitrites Albumin 3.9 g/dL (39 g/L) Urine protein- 2500 mg/g C3 58 mg/dL (580 mg/L) creatinine ratio C4 5.0 mg/dL (50 mg/L) Creatinine 2.6 mg/dL (229.8 umol/L) Which of the following is the most appropriate test to Cryoglobulins Positive perform next? Rheumatoid factor Positive Urinalysis 3+ blood; 3+ protein; ( A) Repeat urinalysis erythrocytes and rare (B) 24-Hour urine collection for total protein erythrocyte casts (C) Sulfosalicylic acid test Urine protein-creatinine ratio 2100 mg/g (D) Urine albumin-creatinine ratio A kidney biopsy is scheduled. (E) Urine protein electrophoresis 114

z Self-Assessment Test ~ Item 84 On physical examination, temperature is 38.5 °C od — P=) (101.3 °F), blood pressure is 90/50 mm Hg, pulse rate is A 52-year-old man is evaluated for a 3-day history of diffuse i= E 89/min, and respiration rate is 22/min. A right internal muscle aches. He has type 2 diabetes mellitus, hyperten- jugular tunneled hemodialysis catheter is in place with no sion, and stage G3 chronic kidney disease. Medications are 7.) wn metformin, valsartan, atorvastatin, calcium, and vitamin D. erythema or discharge at the exit site. A normal-appearing wo nn On physical examination, vital signs are normal. There and functioning left arteriovenous fistula is present. The wn

E 89/min, and respiration rate is 22/min. A right internal muscle aches. He has type 2 diabetes mellitus, hyperten- jugular tunneled hemodialysis catheter is in place with no sion, and stage G3 chronic kidney disease. Medications are 7.) wn metformin, valsartan, atorvastatin, calcium, and vitamin D. erythema or discharge at the exit site. A normal-appearing wo nn On physical examination, vital signs are normal. There and functioning left arteriovenous fistula is present. The wn is significant tenderness over the thighs and arms. The remainder of the examination is normal. a i Blood and urine cultures are obtained. a remainder of the examination is normal. 2) Cefepime and vancomycin are initiated, repeated fluid Laboratory studies: boluses are administered, and intravenous norepinephrine Calcium 8.4 mg/dL (2.1 mmol/L) is started. Creatine kinase 16,200 U/L Creatinine 1.8 mg/dL (159.1 umol/L) Which of the following is the most appropriate additional Electrolytes: management? Sodium 138 mEq/L (138 mmol/L) Potassium 5.2 mEq/L (5.2 mmol/L) (A) Antibiotic lock therapy Chloride 104 mEq/L (104 mmol/L) (B) Arteriovenous fistula excision Bicarbonate 18 mEq/L (18 mmol/L) (C) Exchange the tunneled catheter Phosphorus 6.1 mg/dL (2.0 mmol/L) (D) Remove the tunneled catheter Which of the following is the most likely cause of this patient’s hyperphosphatemia? Item 87 (A) Chronic kidney disease A 24-year-old woman is evaluated during a follow-up visit for (B) Insulin deficiency hypokalemia. She has occasional muscle cramps but no weak- (C) Rhabdomyolysis ness, polyuria, or diarrhea. Medical history is unremarkable. (D) Vitamin D Family history is unobtainable. She takes no medications. On physical examination, blood pressure is 98/68 mm Hg. Other vital signs and the remainder of the examination Item 85 are normal. A 54-year-old man is evaluated for the nephrotic syndrome Laboratory studies: 10 days after undergoing a kidney biopsy. He reports nor- Calcium 10.2 mg/dL (2.55 mmol/L) mal urine volume and no hematuria. He has noticed mild Creatinine 0.9 mg/dL (79.6 umol/L) bilateral flank aches during the past 2 days. Prebiopsy serum Electrolytes: creatinine level was 0.9 mg/dL (79.6 umol/L). Medical his- Sodium 138 mEq/L (138 mmol/L) tory is also significant for hyperlipidemia. Medications are Potassium 3.1 mEq/L (3.1 mmol/L) furosemide and atorvastatin. Chloride 100 mEq/L (100 mmol/L) On physical examination, temperature is 37.0 °C (98.6 °F), Bicarbonate 29 mEq/L (29 mmol/L) blood pressure is 148/88 mm Hg, and pulse rate is 72/min. Bilat- Magnesium 1.4 mg/dL (0.58 mmol/L) eral costovertebral angle tenderness is noted. There is 2+ lower Urine sodium 48 mEq/L (48 mmol/L) extremity edema. The remainder of the examination is normal. Urine potassium 32 mEq/L (32 mmol/L) Laboratory studies show a serum creatinine level of Urine chloride 54 mEq/L (54 mmol/L) 3.2 mg/dL (282.9 pmol/L). Urinalysis shows a specific grav- Urine diuretic screen Negative ity of 1.012; pH of 5.0; 3+ blood; 3+ protein; 1+ leukocytes; Spot urine calcium-creatinine Low >100 erythrocytes/hpf; occasional leukocytes; and no casts. ratio Kidney biopsy shows membranous nephropathy with minimal interstitial fibrosis and no glomerulosclerosis. Which of the following is the most likely diagnosis?

is significant tenderness over the thighs and arms. The remainder of the examination is normal. a i Blood and urine cultures are obtained. a remainder of the examination is normal. 2) Cefepime and vancomycin are initiated, repeated fluid Laboratory studies: boluses are administered, and intravenous norepinephrine Calcium 8.4 mg/dL (2.1 mmol/L) is started. Creatine kinase 16,200 U/L Creatinine 1.8 mg/dL (159.1 umol/L) Which of the following is the most appropriate additional Electrolytes: management? Sodium 138 mEq/L (138 mmol/L) Potassium 5.2 mEq/L (5.2 mmol/L) (A) Antibiotic lock therapy Chloride 104 mEq/L (104 mmol/L) (B) Arteriovenous fistula excision Bicarbonate 18 mEq/L (18 mmol/L) (C) Exchange the tunneled catheter Phosphorus 6.1 mg/dL (2.0 mmol/L) (D) Remove the tunneled catheter Which of the following is the most likely cause of this patient’s hyperphosphatemia? Item 87 (A) Chronic kidney disease A 24-year-old woman is evaluated during a follow-up visit for (B) Insulin deficiency hypokalemia. She has occasional muscle cramps but no weak- (C) Rhabdomyolysis ness, polyuria, or diarrhea. Medical history is unremarkable. (D) Vitamin D Family history is unobtainable. She takes no medications. On physical examination, blood pressure is 98/68 mm Hg. Other vital signs and the remainder of the examination Item 85 are normal. A 54-year-old man is evaluated for the nephrotic syndrome Laboratory studies: 10 days after undergoing a kidney biopsy. He reports nor- Calcium 10.2 mg/dL (2.55 mmol/L) mal urine volume and no hematuria. He has noticed mild Creatinine 0.9 mg/dL (79.6 umol/L) bilateral flank aches during the past 2 days. Prebiopsy serum Electrolytes: creatinine level was 0.9 mg/dL (79.6 umol/L). Medical his- Sodium 138 mEq/L (138 mmol/L) tory is also significant for hyperlipidemia. Medications are Potassium 3.1 mEq/L (3.1 mmol/L) furosemide and atorvastatin. Chloride 100 mEq/L (100 mmol/L) On physical examination, temperature is 37.0 °C (98.6 °F), Bicarbonate 29 mEq/L (29 mmol/L) blood pressure is 148/88 mm Hg, and pulse rate is 72/min. Bilat- Magnesium 1.4 mg/dL (0.58 mmol/L) eral costovertebral angle tenderness is noted. There is 2+ lower Urine sodium 48 mEq/L (48 mmol/L) extremity edema. The remainder of the examination is normal. Urine potassium 32 mEq/L (32 mmol/L) Laboratory studies show a serum creatinine level of Urine chloride 54 mEq/L (54 mmol/L) 3.2 mg/dL (282.9 pmol/L). Urinalysis shows a specific grav- Urine diuretic screen Negative ity of 1.012; pH of 5.0; 3+ blood; 3+ protein; 1+ leukocytes; Spot urine calcium-creatinine Low >100 erythrocytes/hpf; occasional leukocytes; and no casts. ratio Kidney biopsy shows membranous nephropathy with minimal interstitial fibrosis and no glomerulosclerosis. Which of the following is the most likely diagnosis? (A) Gitelman syndrome Which of the following is the most appropriate diagnostic test to perform next? (B) Laxative abuse (C) Primary hyperaldosteronism (A) Anti-phospholipase receptor A2 antibody measurement (D) Surreptitious vomiting (B) Fractional excretion of sodium (C) Radionuclide imaging (D) Renal ultrasonography with Doppler Item 88 A 45-year-old man is evaluated during a routine follow-up visit for stage G3 chronic kidney disease. He also has hyper- Item 86 tension and type 2 diabetes mellitus. Medications are chole- A 27-year-old man is evaluated in the ICU for septic shock. calciferol, hydrochlorothiazide, metformin, canagliflozin, For the past 3 months, he has received dialysis for end-stage and valsartan. kidney disease with a tunneled catheter because his arterio On physical examination, blood pressure is 140/80 mm venous fistula has not matured for use. He reports a 1-day Hg; other vital signs are normal. The remainder of the exam- history of fever and malaise. ination is normal.

72) @o =a His calculated 10-year risk of an atherosclerotic cardio- Laboratory studies: > vascular disease event is 7.5%. 7.) Electrolytes: wn o Laboratory studies: Sodium 118 mEq/L (118 mmol/L) ~” wn Total cholesterol 186 mg/dL (4.8 mmol/L) Potassium 3.1 mEq/L (3.1 mmol/L) 4 HDL cholesterol 34 mg/dL (0.88 mmol/L) Chloride 90 mEq/L (90 mmol/L) © Ss LDL cholesterol 113 mg/dL (2.9 mmol/L) Bicarbonate 22 mEq/L (22 mmol/L) Osmolality 248 mOsm/kg H,O -- Creatinine 2.0 mg/dL (176.8 mol/L) o 2) Estimated glomerular 47 mL/min/1.73 m? - Which of the following is the most appropriate treatment? filtration rate (A) Fluid restriction Which of the following is the most appropriate (B) 0.9% saline treatment to reduce this patient’s risk for atherosclerotic cardiovascular disease? (C) 3% saline plus desmopressin (D) Tolvaptan (A) Evolocumab (B) Ezetimibe (C) High-intensity rosuvastatin Item 91 (D) Moderate-intensity atorvastatin A 41-year-old woman is evaluated during a follow-up visit for stage 2 hypertension confirmed by daytime ambulatory blood pressure monitoring. She also has a 10-year history of Item 89 type 2 diabetes mellitus and hyperlipidemia. Medications are atorvastatin, metformin, and empagliflozin. A 33-year-old woman is evaluated in the hospital follow- On physical examination, blood pressure is 142/92 mm ing a recent diagnosis of membranoproliferative glomer- Hg, and pulse rate is 72/min; other vital signs are normal. BMI ulonephritis. She engages in transactional sex. She has no is 28. The remainder of the examination is unremarkable. other medical problems and takes no medications. Laboratory studies show a serum creatinine level of On physical examination, blood pressure is 142/90 mm Hg; other vital signs are normal. There is 1-mm pitting 0.9 mg/dL (79.6 umol/L). Urine dipstick reveals no blood or protein. edema of the ankles bilaterally. The remainder of the exam- The patient is instructed in lifestyle modifications for ination is unremarkable. blood pressure control. Laboratory studies: G3 69 mg/dL (690 mg/L) Which of the following is the most appropriate additional C4 5 mg/dL (50 mg/L) management? Creatinine 2.5 mg/dL (221 umol/L) Antinuclear antibodies Negative (A) Begin amlodipine Antimyeloperoxidase antibodies Negative (B) Begin hydrochlorothiazide Antiproteinase-3 antibodies Negative (C) Continue nonpharmacologic therapy with blood pres- Fourth-generation HIV test Negative sure measurement in 3 months Urinalysis 3+ blood; 2+ protein Urine protein-creatinine ratio 1700 mg/g (D) Obtain urine albumin-creatinine ratio

72) @o =a His calculated 10-year risk of an atherosclerotic cardio- Laboratory studies: > vascular disease event is 7.5%. 7.) Electrolytes: wn o Laboratory studies: Sodium 118 mEq/L (118 mmol/L) ~” wn Total cholesterol 186 mg/dL (4.8 mmol/L) Potassium 3.1 mEq/L (3.1 mmol/L) 4 HDL cholesterol 34 mg/dL (0.88 mmol/L) Chloride 90 mEq/L (90 mmol/L) © Ss LDL cholesterol 113 mg/dL (2.9 mmol/L) Bicarbonate 22 mEq/L (22 mmol/L) Osmolality 248 mOsm/kg H,O -- Creatinine 2.0 mg/dL (176.8 mol/L) o 2) Estimated glomerular 47 mL/min/1.73 m? - Which of the following is the most appropriate treatment? filtration rate (A) Fluid restriction Which of the following is the most appropriate (B) 0.9% saline treatment to reduce this patient’s risk for atherosclerotic cardiovascular disease? (C) 3% saline plus desmopressin (D) Tolvaptan (A) Evolocumab (B) Ezetimibe (C) High-intensity rosuvastatin Item 91 (D) Moderate-intensity atorvastatin A 41-year-old woman is evaluated during a follow-up visit for stage 2 hypertension confirmed by daytime ambulatory blood pressure monitoring. She also has a 10-year history of Item 89 type 2 diabetes mellitus and hyperlipidemia. Medications are atorvastatin, metformin, and empagliflozin. A 33-year-old woman is evaluated in the hospital follow- On physical examination, blood pressure is 142/92 mm ing a recent diagnosis of membranoproliferative glomer- Hg, and pulse rate is 72/min; other vital signs are normal. BMI ulonephritis. She engages in transactional sex. She has no is 28. The remainder of the examination is unremarkable. other medical problems and takes no medications. Laboratory studies show a serum creatinine level of On physical examination, blood pressure is 142/90 mm Hg; other vital signs are normal. There is 1-mm pitting 0.9 mg/dL (79.6 umol/L). Urine dipstick reveals no blood or protein. edema of the ankles bilaterally. The remainder of the exam- The patient is instructed in lifestyle modifications for ination is unremarkable. blood pressure control. Laboratory studies: G3 69 mg/dL (690 mg/L) Which of the following is the most appropriate additional C4 5 mg/dL (50 mg/L) management? Creatinine 2.5 mg/dL (221 umol/L) Antinuclear antibodies Negative (A) Begin amlodipine Antimyeloperoxidase antibodies Negative (B) Begin hydrochlorothiazide Antiproteinase-3 antibodies Negative (C) Continue nonpharmacologic therapy with blood pres- Fourth-generation HIV test Negative sure measurement in 3 months Urinalysis 3+ blood; 2+ protein Urine protein-creatinine ratio 1700 mg/g (D) Obtain urine albumin-creatinine ratio Kidney biopsy showed membranoproliferative glomer- ulonephritis with positive immunofluorescence staining for Item 92 IgG, IgM, Clq, and C3. A 52-year-old woman is evaluated in the emergency depart ment for abdominal pain and metabolic acidosis. The patient Which of the following is the most likely cause of this has been drinking alcohol steadily for 1 week and has been patient’s glomerulonephritis? brought to the emergency department by friends. The patient (A) Genetic mutations of alternative complement path- also had episodes of nausea and vomiting and abdominal way proteins pain over the past 24 to 48 hours. The patient was hospitalized (B) Hepatitis B virus infection 1 year ago with isopropyl alcohol intoxication. She reports no other medical problems and takes no medications. (C) Hepatitis C virus infection On physical examination, blood pressure is 110/72 mm (D) Syphilis Hg, pulse rate is 110/min, and respiration rate is 20/min. BMI is 18. Abdominal examination reveals diffuse tenderness to palpation. The remainder of the examination is normal. Item 90 Laboratory studies: A 44-year-old woman is evaluated in the emergency depart- Blood urea nitrogen 32 mg/ dL (11.4 mmol/L) ment for confusion. Previous history is unknown. Electrolytes: On physical examination, vital signs are normal. She is Sodium 139 mEq/L (139 mmol/L) oriented to her name only. Pulmonary and cardiovascular Potassium 3.9 mEq/L (3.9 mmol/L) examinations are normal. The patient has confusion, but the Chloride 100 mEq/L (100 mmol/L) neurologic examination is otherwise unremarkable. Bicarbonate 11 mEq/L (1. mmol/L)

Kidney biopsy showed membranoproliferative glomer- ulonephritis with positive immunofluorescence staining for Item 92 IgG, IgM, Clq, and C3. A 52-year-old woman is evaluated in the emergency depart ment for abdominal pain and metabolic acidosis. The patient Which of the following is the most likely cause of this has been drinking alcohol steadily for 1 week and has been patient’s glomerulonephritis? brought to the emergency department by friends. The patient (A) Genetic mutations of alternative complement path- also had episodes of nausea and vomiting and abdominal way proteins pain over the past 24 to 48 hours. The patient was hospitalized (B) Hepatitis B virus infection 1 year ago with isopropyl alcohol intoxication. She reports no other medical problems and takes no medications. (C) Hepatitis C virus infection On physical examination, blood pressure is 110/72 mm (D) Syphilis Hg, pulse rate is 110/min, and respiration rate is 20/min. BMI is 18. Abdominal examination reveals diffuse tenderness to palpation. The remainder of the examination is normal. Item 90 Laboratory studies: A 44-year-old woman is evaluated in the emergency depart- Blood urea nitrogen 32 mg/ dL (11.4 mmol/L) ment for confusion. Previous history is unknown. Electrolytes: On physical examination, vital signs are normal. She is Sodium 139 mEq/L (139 mmol/L) oriented to her name only. Pulmonary and cardiovascular Potassium 3.9 mEq/L (3.9 mmol/L) examinations are normal. The patient has confusion, but the Chloride 100 mEq/L (100 mmol/L) neurologic examination is otherwise unremarkable. Bicarbonate 11 mEq/L (1. mmol/L) 116

_ Self-Assessment Test et On physical examination, blood pressure is 160/72 mm ct Ethanol 40 mg/dL (8.64 mmol/L) —_ aot Hg, and pulse rate is 60/min; other vital signs are normal. i Glucose 72 mg/dL (4.0 mmol/L) = CONT. Cardiac examination reveals an S,. The remainder of the Plasma osmolality 290 mOsm/kg H,O examination is noncontributory. Urinalysis Specific gravity 1.030; pH 5.5; 2) wn ao no blood; trace ketones Laboratory studies: wn Calcium 9.4 mg/dL (2.4 mmol/L) wn

On physical examination, blood pressure is 160/72 mm ct Ethanol 40 mg/dL (8.64 mmol/L) —_ aot Hg, and pulse rate is 60/min; other vital signs are normal. i Glucose 72 mg/dL (4.0 mmol/L) = CONT. Cardiac examination reveals an S,. The remainder of the Plasma osmolality 290 mOsm/kg H,O examination is noncontributory. Urinalysis Specific gravity 1.030; pH 5.5; 2) wn ao no blood; trace ketones Laboratory studies: wn Calcium 9.4 mg/dL (2.4 mmol/L) wn Which of the following is the most likely diagnosis? Creatinine 2.3 mg/dL (203.3 pmol/L) = — Potassium 4.7 mEq/L (4.7 mmol/L) 7) (A) Alcoholic ketoacidosis i?) Phosphorus 4.4 mg/dL (1.4 mmol/L) (B) Ethylene glycol toxicity Estimated glomerular 26 mL/min/1.73 m? (C) Isopropyl alcohol toxicity filtration rate (D) Methanol toxicity Which of the following is the most appropriate management?

Which of the following is the most likely diagnosis? Creatinine 2.3 mg/dL (203.3 pmol/L) = — Potassium 4.7 mEq/L (4.7 mmol/L) 7) (A) Alcoholic ketoacidosis i?) Phosphorus 4.4 mg/dL (1.4 mmol/L) (B) Ethylene glycol toxicity Estimated glomerular 26 mL/min/1.73 m? (C) Isopropyl alcohol toxicity filtration rate (D) Methanol toxicity Which of the following is the most appropriate management? Item 93 (A) Adda phosphate binder A 32-year-old man is evaluated during a follow-up visit (B) Discontinue all medications except insulin after passing his third calcium oxalate kidney stone in (C) Intensify hypertension management 4 years despite maintaining a high urine volume. He has no (D) Refer for hospice care other medical problems. His only medication is potassium citrate, which was initiated after passing the most recent stone. He drinks 4 cups of coffee daily and typically eats Item 95 meals at fast-food restaurants. Physical examination findings, including vital signs, A 32-year-old woman is seen following evaluation for a are normal. single episode of painless hematuria that she noted last week. She has chronic kidney disease secondary to chronic Laboratory studies: tubulointerstitial nephritis confirmed by biopsy. She took 24-Hour urine studies: Chinese herbal weight loss pills daily for 3 years. She took Volume 2600 mL acetaminophen or ibuprofen for arthralgia three or four pH 6.5 times monthly for 5 years. Since the kidney biopsy, she has Calcium 295 mg (normal range, discontinued all drugs and supplements. She has no other 50-300 mg) medical problems. Citrate 850 mg (normal range, The physical examination, including vital signs, is 100-300 mg) normal. Oxalate 35 mg (normal range, 10-40 mg) Uric acid 640 mg (normal range, Urinalysis shows a specific gravity of 1.012, 3+ blood,

Item 93 (A) Adda phosphate binder A 32-year-old man is evaluated during a follow-up visit (B) Discontinue all medications except insulin after passing his third calcium oxalate kidney stone in (C) Intensify hypertension management 4 years despite maintaining a high urine volume. He has no (D) Refer for hospice care other medical problems. His only medication is potassium citrate, which was initiated after passing the most recent stone. He drinks 4 cups of coffee daily and typically eats Item 95 meals at fast-food restaurants. Physical examination findings, including vital signs, A 32-year-old woman is seen following evaluation for a are normal. single episode of painless hematuria that she noted last week. She has chronic kidney disease secondary to chronic Laboratory studies: tubulointerstitial nephritis confirmed by biopsy. She took 24-Hour urine studies: Chinese herbal weight loss pills daily for 3 years. She took Volume 2600 mL acetaminophen or ibuprofen for arthralgia three or four pH 6.5 times monthly for 5 years. Since the kidney biopsy, she has Calcium 295 mg (normal range, discontinued all drugs and supplements. She has no other 50-300 mg) medical problems. Citrate 850 mg (normal range, The physical examination, including vital signs, is 100-300 mg) normal. Oxalate 35 mg (normal range, 10-40 mg) Uric acid 640 mg (normal range, Urinalysis shows a specific gravity of 1.012, 3+ blood, 250-750 mg) 1+ protein, 1+ leukocytes, 25-50 nondysmorphic erythro- cytes/hpf, 3-5 leukocytes/hpf, and no casts; urine culture The patient is counseled to start a low sodium diet. is negative. CT scan of the abdomen and pelvis shows normal kid- Which of the following is the most appropriate additional neys and collecting system. management? Which of the following is the most appropriate (A) Decrease calcium intake management? (B) Decrease coffee intake C) 2 Decrease oxalate intake (A) Cystoscopy with retrograde pyelography

250-750 mg) 1+ protein, 1+ leukocytes, 25-50 nondysmorphic erythro- cytes/hpf, 3-5 leukocytes/hpf, and no casts; urine culture The patient is counseled to start a low sodium diet. is negative. CT scan of the abdomen and pelvis shows normal kid- Which of the following is the most appropriate additional neys and collecting system. management? Which of the following is the most appropriate (A) Decrease calcium intake management? (B) Decrease coffee intake C) 2 Decrease oxalate intake (A) Cystoscopy with retrograde pyelography Start allopurinol (B) MRI of the kidneys Bes Start chlorthalidone (C) Renal angiography (D) Observation

250-750 mg) 1+ protein, 1+ leukocytes, 25-50 nondysmorphic erythro- cytes/hpf, 3-5 leukocytes/hpf, and no casts; urine culture The patient is counseled to start a low sodium diet. is negative. CT scan of the abdomen and pelvis shows normal kid- Which of the following is the most appropriate additional neys and collecting system. management? Which of the following is the most appropriate (A) Decrease calcium intake management? (B) Decrease coffee intake C) 2 Decrease oxalate intake (A) Cystoscopy with retrograde pyelography Start allopurinol (B) MRI of the kidneys Bes Start chlorthalidone (C) Renal angiography (D) Observation Item 94 An 84-year-old woman is evaluated during a follow-up Item 96 visit for stage G4 chronic kidney disease. Her only symp- A 69-year-old man is evaluated 7 days after starting nafcillin tom is lack of energy. She is independent in her activi- to treat a culture-proven methicillin-sensitive Staphylo ties of daily living. She has declined renal replacement coccal aureus sternal wound infection. The infection was therapy after attending a dialysis education class. She diagnosed 10 days after coronary artery bypass surgery. understands the process and purpose of dialysis and the History is significant for diabetes mellitus. Other medica consequence of non-treatment but prefers non-dialytic tions are aspirin, metformin, metoprolol, atorvastatin, and therapy. Medical history is also significant for diabetes acetaminophen as needed. mellitus, heart failure, hypertension, and stroke. Med- On physical examination, vital signs are normal. The ications are furosemide, lisinopril, hydralazine, insulin sternal wound appears to be healing, with minimal tender aspart, insulin detemir, nifedipine, metoprolol, and aspi- ness and redness and decreased drainage. The remainder of rin, 81 mg. the examination is unremarkable.

Item 94 An 84-year-old woman is evaluated during a follow-up Item 96 visit for stage G4 chronic kidney disease. Her only symp- A 69-year-old man is evaluated 7 days after starting nafcillin tom is lack of energy. She is independent in her activi- to treat a culture-proven methicillin-sensitive Staphylo ties of daily living. She has declined renal replacement coccal aureus sternal wound infection. The infection was therapy after attending a dialysis education class. She diagnosed 10 days after coronary artery bypass surgery. understands the process and purpose of dialysis and the History is significant for diabetes mellitus. Other medica consequence of non-treatment but prefers non-dialytic tions are aspirin, metformin, metoprolol, atorvastatin, and therapy. Medical history is also significant for diabetes acetaminophen as needed. mellitus, heart failure, hypertension, and stroke. Med- On physical examination, vital signs are normal. The ications are furosemide, lisinopril, hydralazine, insulin sternal wound appears to be healing, with minimal tender aspart, insulin detemir, nifedipine, metoprolol, and aspi- ness and redness and decreased drainage. The remainder of rin, 81 mg. the examination is unremarkable. 117

Self-Assessment Test 172) @o sy Laboratory studies: steroid use. His medical history is otherwise unremarkable, ~ G 61 mg/dL (610 mg/L) and he takes no prescribed medications. wn” 7.) CONT. C4 On physical examination, vital signs are normal. BMI @o 13 mg/dL (130 mg/L) wn wn Creatinine 2.0 mg/dL (176.8 umol/L); before hospital is 29. The patient is muscular, with no evidence of subcuta- 5 admission: 0.9 mg/dL (79.6 umol/L) neous fat. He has mild muscle tenderness in the right lower @ =} Urinalysis 3+ blood; 2+ protein; 30-40 erythrocytes back. The remainder of the examination is unremarkable. oe —] hpf; 2-5 leukocytes/hpf; dysmorphic @ wn erythrocytes; rare erythrocyte casts Which of the following is the most appropriate test to - Kidney biopsy shows a mild proliferative glomerulo perform next? nephritis with infiltrating neutrophils, granular C3, and IgG (A) Blood urea nitrogen measurement and IgM staining on immunofluorescence; hump-shaped (B) Creatinine clearance subepithelial electron-dense deposits are seen on electron (C) Radionuclide imaging microscopy. (D) Serum cystatin C measurement Which of the following is the most appropriate treatment?

Kidney biopsy shows a mild proliferative glomerulo perform next? nephritis with infiltrating neutrophils, granular C3, and IgG (A) Blood urea nitrogen measurement and IgM staining on immunofluorescence; hump-shaped (B) Creatinine clearance subepithelial electron-dense deposits are seen on electron (C) Radionuclide imaging microscopy. (D) Serum cystatin C measurement Which of the following is the most appropriate treatment? (A) Add lisinopril Item 99 (B) Add prednisone A 67-year-old man is evaluated during a follow-up visit (C) Continue nafcillin 4 weeks after being diagnosed with the nephrotic syndrome. He has a 7-year history of well-controlled type 2 diabetes (D) Initiate sodium restriction and furosemide mellitus with no retinopathy, neuropathy, or clinically evi- dent vascular disease. He has no other medical problems, and his only medication is metformin. Item 97 On physical examination, blood pressure is 110/60 mm A 37-year-old woman is evaluated for a new-onset head- Hg; other vital signs are normal. No rash is noted. There is 2-mm ache. She describes the headache as a steady pain located pitting edema in the lower extremities to the knees bilaterally. in the front of her head, bilaterally, and not associated with Laboratory studies: any other symptoms. The headache has been present for Albumin 2.1 g/dL (21 g/L) more than 24 hours. She is in the third trimester of her first Total cholesterol 330 mg/dL (8.5 mmol/L) pregnancy. Until now, her pregnancy has been unremark- able and she has otherwise been healthy. Creatinine 1.4 mg/dL (123.8 pmol/L) On physical examination, blood pressure is 145/95 mm (4 months ago, 1.0 mg/dL Hg; other vital signs are normal. There is no papilledema. [88.4 umol/L]) Hemoglobin A,, 6.9% On abdominal examination, the patient has a gravid uterus Serum protein Negative consistent with her stage of pregnancy, and there is no electrophoresis abdominal tenderness. Neurologic examination is normal. 24-Hour urine protein 12,000 mg/24h Laboratory studies: excretion Hemoglobin 12.3 g/dL (123 g/L) Platelet count 156,000/uL (156 x 10°/L) Kidney biopsy shows expansion of the mesangial areas Alanine aminotransferase Normal by deposits of homogenous, pale eosinophilic material that Aspartate aminotransferase Normal are positive with Congo red staining and demonstrate apple- Creatinine 1.4 mg/dL (123.8 pmol/L) green birefringence when viewed under polarized light. Random urine protein- 125 mg/g creatinine ratio Which of the following is the most likely diagnosis?

(A) Add lisinopril Item 99 (B) Add prednisone A 67-year-old man is evaluated during a follow-up visit (C) Continue nafcillin 4 weeks after being diagnosed with the nephrotic syndrome. He has a 7-year history of well-controlled type 2 diabetes (D) Initiate sodium restriction and furosemide mellitus with no retinopathy, neuropathy, or clinically evi- dent vascular disease. He has no other medical problems, and his only medication is metformin. Item 97 On physical examination, blood pressure is 110/60 mm A 37-year-old woman is evaluated for a new-onset head- Hg; other vital signs are normal. No rash is noted. There is 2-mm ache. She describes the headache as a steady pain located pitting edema in the lower extremities to the knees bilaterally. in the front of her head, bilaterally, and not associated with Laboratory studies: any other symptoms. The headache has been present for Albumin 2.1 g/dL (21 g/L) more than 24 hours. She is in the third trimester of her first Total cholesterol 330 mg/dL (8.5 mmol/L) pregnancy. Until now, her pregnancy has been unremark- able and she has otherwise been healthy. Creatinine 1.4 mg/dL (123.8 pmol/L) On physical examination, blood pressure is 145/95 mm (4 months ago, 1.0 mg/dL Hg; other vital signs are normal. There is no papilledema. [88.4 umol/L]) Hemoglobin A,, 6.9% On abdominal examination, the patient has a gravid uterus Serum protein Negative consistent with her stage of pregnancy, and there is no electrophoresis abdominal tenderness. Neurologic examination is normal. 24-Hour urine protein 12,000 mg/24h Laboratory studies: excretion Hemoglobin 12.3 g/dL (123 g/L) Platelet count 156,000/uL (156 x 10°/L) Kidney biopsy shows expansion of the mesangial areas Alanine aminotransferase Normal by deposits of homogenous, pale eosinophilic material that Aspartate aminotransferase Normal are positive with Congo red staining and demonstrate apple- Creatinine 1.4 mg/dL (123.8 pmol/L) green birefringence when viewed under polarized light. Random urine protein- 125 mg/g creatinine ratio Which of the following is the most likely diagnosis? Which of the following is the most likely diagnosis? (A) Diabetic kidney disease (B) IgA nephropathy (A) Acute fatty liver of pregnancy (C) Membranous nephropathy (B) Migraine headache (D) Renal AL amyloidosis (C) Pheochromocytoma (D) Preeclampsia Item 100 An 81-year-old woman is evaluated in the emergency Item 98 department for abrupt onset of lower extremity edema A 26-year-old man is referred for an elevated serum creat- that began 2 weeks ago and has progressed to generalized inine level of 1.4 mg/dL (123.8 umol/L) that was measured edema. Medical history is significant for hypertension. Her when he presented to an urgent care center for flank pain. only medication is amlodipine. The flank pain was determined to be musculoskeletal and On physical examination, vital signs are normal. There caused by a weight-lifting injury. A subsequent urinalysis is periorbital edema, ascites, and pitting edema of the fore- was normal, and a random urine albumin-creatinine ratio arms and lower extremities to the thighs. The remainder of was 10 mg/g. He reports that he takes no creatine sup- the examination, including cardiovascular and pulmonary plements but is evasive when questioned about anabolic examinations, is unremarkable.

Which of the following is the most likely diagnosis? (A) Diabetic kidney disease (B) IgA nephropathy (A) Acute fatty liver of pregnancy (C) Membranous nephropathy (B) Migraine headache (D) Renal AL amyloidosis (C) Pheochromocytoma (D) Preeclampsia Item 100 An 81-year-old woman is evaluated in the emergency Item 98 department for abrupt onset of lower extremity edema A 26-year-old man is referred for an elevated serum creat- that began 2 weeks ago and has progressed to generalized inine level of 1.4 mg/dL (123.8 umol/L) that was measured edema. Medical history is significant for hypertension. Her when he presented to an urgent care center for flank pain. only medication is amlodipine. The flank pain was determined to be musculoskeletal and On physical examination, vital signs are normal. There caused by a weight-lifting injury. A subsequent urinalysis is periorbital edema, ascites, and pitting edema of the fore- was normal, and a random urine albumin-creatinine ratio arms and lower extremities to the thighs. The remainder of was 10 mg/g. He reports that he takes no creatine sup- the examination, including cardiovascular and pulmonary plements but is evasive when questioned about anabolic examinations, is unremarkable. 118

7 Self-Assessment Test ~ ef Laboratory studies: On physical examination, vital signs are normal. — ~~ Albumin 1.6 g/dL (16 g/L) Abdominal examination reveals a palpable kidney on = Total cholesterol Creatinine 364 mg/dL (9.4 mmol/L) 2.8 mg/dL (248 umol/L); 2 months the right side. The remainder of the examination is unre- markable. FS wn wn ago: 0.7 mg/dL (61.9 umol/L) Laboratory studies show a serum creatinine level of ae wn Urinalysis No blood; 4+ protein 1.3 mg/dL (114.9 umol/L), representing a decrease in esti- wn mated glomerular filtration rate of >5 mL/min/1.73 m? from = Kidney ultrasound with Doppler shows normal-sized = 1 year ago. Liver chemistry tests are normal. CF) echogenic kidneys with no hydronephrosis; there are no rn

mated glomerular filtration rate of >5 mL/min/1.73 m? from = Kidney ultrasound with Doppler shows normal-sized = 1 year ago. Liver chemistry tests are normal. CF) echogenic kidneys with no hydronephrosis; there are no rn abnormalities on Doppler flow. Which of the following is the most appropriate management? Which of the following is the most likely diagnosis? (A) Discontinue lisinopril; start telmisartan (A) ANCA-associated glomerulonephritis (B) Obtain ultrasonography of the kidneys (B) Anti-glomerular basement membrane antibody disease (C) Start octreotide (C) Membranous nephropathy (D) Start tolvaptan (D) Minimal change glomerulopathy

abnormalities on Doppler flow. Which of the following is the most appropriate management? Which of the following is the most likely diagnosis? (A) Discontinue lisinopril; start telmisartan (A) ANCA-associated glomerulonephritis (B) Obtain ultrasonography of the kidneys (B) Anti-glomerular basement membrane antibody disease (C) Start octreotide (C) Membranous nephropathy (D) Start tolvaptan (D) Minimal change glomerulopathy Item 101 Item 103 An 87-year-old man is hospitalized for the inability to void. A 45-year-old woman is evaluated during a follow-up visit He has a 4-year history of urinary hesitancy and dribbling. for newly diagnosed severe hypertension. She began low- He lives alone with the assistance of a nephew but finds it dose hydrochlorothiazide and amlodipine therapy 1 month increasingly difficult to live independently. He has no other ago. There is no family history of hypertension. She has no medical history and takes no medications. other medical problems and takes no other medications. On physical examination, he is thin and frail appearing. On physical examination, blood pressure is 164/100 mm Blood pressure is 158/64 mm Hg, and pulse rate is 78/min Hg in both arms, pulse rate is 76/min, and respiration rate is without orthostatic changes. BMI is 22. The prostate is dif 18/min. BMIis 24. The remainder of the examination is normal. fusely enlarged. There is 1+ lower extremity edema. Gener- Laboratory studies: alized weakness is noted. The remainder of the examination Bicarbonate 30 mEq/L (30 mmol/L) is unremarkable. Creatinine 0.9 mg/dL (79.6 pmol/L) A bladder catheter drains 850 mL of urine. Potassium 2.9 mEq/L (2.9 mmol/L) Laboratory studies show a blood urea nitrogen level Sodium 138 mEq/L (138 mmol/L) of 133 mg/dL (47.5 mmol/L) and a serum creatinine level of Urinalysis No blood or protein 8.9 mg/dL (786.8 mol/L). Kidney ultrasound shows an 8.3-cm right kidney anda Which of the following is the most appropriate diagnostic 7.9-cm left kidney, marked cortical echogenicity and thin test to perform next? ning, and moderate-severe hydronephrosis. During the first 24 hours, urine output with the bladder (A) Plasma aldosterone concentration/plasma renin catheter in place is 1240 mL. Follow-up bladder ultrasound activity ratio shows less than 50 mL of residual urine. On hospital day 2 (B) Plasma fractionated metanephrines measurement the urine output is 340 mL. (C) Renal artery CT angiography On hospital day 3, the serum creatinine level is (D) 24-Hour urine free cortisol measurement 8.2 mg/dL (724.8 pmol/L). Repeat kidney ultrasound shows persistent hydronephrosis.

Item 101 Item 103 An 87-year-old man is hospitalized for the inability to void. A 45-year-old woman is evaluated during a follow-up visit He has a 4-year history of urinary hesitancy and dribbling. for newly diagnosed severe hypertension. She began low- He lives alone with the assistance of a nephew but finds it dose hydrochlorothiazide and amlodipine therapy 1 month increasingly difficult to live independently. He has no other ago. There is no family history of hypertension. She has no medical history and takes no medications. other medical problems and takes no other medications. On physical examination, he is thin and frail appearing. On physical examination, blood pressure is 164/100 mm Blood pressure is 158/64 mm Hg, and pulse rate is 78/min Hg in both arms, pulse rate is 76/min, and respiration rate is without orthostatic changes. BMI is 22. The prostate is dif 18/min. BMIis 24. The remainder of the examination is normal. fusely enlarged. There is 1+ lower extremity edema. Gener- Laboratory studies: alized weakness is noted. The remainder of the examination Bicarbonate 30 mEq/L (30 mmol/L) is unremarkable. Creatinine 0.9 mg/dL (79.6 pmol/L) A bladder catheter drains 850 mL of urine. Potassium 2.9 mEq/L (2.9 mmol/L) Laboratory studies show a blood urea nitrogen level Sodium 138 mEq/L (138 mmol/L) of 133 mg/dL (47.5 mmol/L) and a serum creatinine level of Urinalysis No blood or protein 8.9 mg/dL (786.8 mol/L). Kidney ultrasound shows an 8.3-cm right kidney anda Which of the following is the most appropriate diagnostic 7.9-cm left kidney, marked cortical echogenicity and thin test to perform next? ning, and moderate-severe hydronephrosis. During the first 24 hours, urine output with the bladder (A) Plasma aldosterone concentration/plasma renin catheter in place is 1240 mL. Follow-up bladder ultrasound activity ratio shows less than 50 mL of residual urine. On hospital day 2 (B) Plasma fractionated metanephrines measurement the urine output is 340 mL. (C) Renal artery CT angiography On hospital day 3, the serum creatinine level is (D) 24-Hour urine free cortisol measurement 8.2 mg/dL (724.8 pmol/L). Repeat kidney ultrasound shows persistent hydronephrosis. Which of the following is the most appropriate next step in Item 104 management? A 23-year-old woman is evaluated during a follow-up visit for focal segmental glomerulosclerosis that was diagnosed (A) Discuss goals of care 3 weeks ago. The edema in her lower extremities has not (B) Initiate intravenous 0.9% saline improved on her current regimen of prednisone, losartan, (C) Obtain noncontrast CT of abdomen and pelvis atorvastatin, and maximal doses of oral furosemide. (D) Place bilateral ureteral stents On physical examination, vital signs are normal. The patient weighs 72 kg (158.7 lb). There is 3-mm pitting edema of the lower extremities through the mid-thigh, equal on both Item 102 sides. The remainder of the examination is unremarkable. A 31-year-old woman is evaluated during a follow-up visit Laboratory studies: for progressive autosomal dominant polycystic kidney dis- 2.0 g/dL (20 g/L) Albumin ease. She has a recent history of an infected kidney cyst. Total cholesterol 303 mg/dL (7.8 mmol/L) She also has hypertension. Family history is significant for Creatinine 0.6 mg/dL (53 pmol/L) end-stage kidney disease in her father at 50 years of age due 9150 mg/g Urine protein-creatinine ratio to autosomal dominant polycystic kidney disease. Her only medication is lisinopril. CT of the chest is normal.

Which of the following is the most appropriate next step in Item 104 management? A 23-year-old woman is evaluated during a follow-up visit for focal segmental glomerulosclerosis that was diagnosed (A) Discuss goals of care 3 weeks ago. The edema in her lower extremities has not (B) Initiate intravenous 0.9% saline improved on her current regimen of prednisone, losartan, (C) Obtain noncontrast CT of abdomen and pelvis atorvastatin, and maximal doses of oral furosemide. (D) Place bilateral ureteral stents On physical examination, vital signs are normal. The patient weighs 72 kg (158.7 lb). There is 3-mm pitting edema of the lower extremities through the mid-thigh, equal on both Item 102 sides. The remainder of the examination is unremarkable. A 31-year-old woman is evaluated during a follow-up visit Laboratory studies: for progressive autosomal dominant polycystic kidney dis- 2.0 g/dL (20 g/L) Albumin ease. She has a recent history of an infected kidney cyst. Total cholesterol 303 mg/dL (7.8 mmol/L) She also has hypertension. Family history is significant for Creatinine 0.6 mg/dL (53 pmol/L) end-stage kidney disease in her father at 50 years of age due 9150 mg/g Urine protein-creatinine ratio to autosomal dominant polycystic kidney disease. Her only medication is lisinopril. CT of the chest is normal. 119

.%e) 2. Laboratory studies: = b= Creatinine 1.6 mg/dL (141.4 umol/L) wn wn (A) Add metolazone Electrolytes: @o i) (B) Administer furosemide by continuous intravenous Sodium 136 mEq/L (136 mmol/L) = infusion Potassium 5.6 mEq/L (5.5 mmol/L) @o = (C) Administer furosemide by intravenous bolus Chloride 104 mEq/L (104 mmol/L) “ (D) Discontinue prednisone; add cyclosporine Bicarbonate 24 mEq/L (24 mmol/L) ry Urine albumin-creatinine ratio 320 mg/g wn oe (E) Hemodialysis with ultrafiltration ECG is normal. The patient is counseled to start a low potassium diet. Item 105 A 33-year-old man is evaluated for acute kidney injury Which of the following is the most appropriate management? 48 hours after being hospitalized for herpes simplex (A) Add hydrochlorothiazide virus encephalitis. Diagnosis was confirmed with poly- (B) Add patiromer merase chain reaction testing of the cerebrospinal fluid. He is being treated with intravenous high-dose acyclo (C) Administer intravenous calcium gluconate vir. Empiric therapy with ceftriaxone plus vancomycin (D) No further treatment was initiated and then discontinued after the results of the cerebrospinal fluid analysis became available. Medical Item 107 history is significant for chronic kidney disease due to hereditary nephritis and hypertension. Outpatient medi A 31-year-old woman seeks preconception counseling. She cations are lisinopril and hydrochlorothiazide, both held has systemic lupus erythematosus and lupus nephritis, both since admission. of which have been stable for the past year; she has had no On physical examination, vital signs are normal. The proteinuria for more than 12 months. She currently feels patient has some difficulty with attention and orientation to well. Medications are mycophenolate mofetil, hydroxychlo- time but is otherwise neurologically intact. The remainder roquine, and low-dose prednisone. of the examination is normal. Physical examination findings, including vital signs, are normal. Current laboratory studies: Creatinine 2.3 mg/dL (203.3 umol/L); Which of the following medications should be baseline: 1.8 mg/dL (159.1 umol/L) discontinued in this patient before conception? Electrolytes: Sodium 137 mEq/L (137 mmol/L) (A) Hydroxychloroquine Potassium 5.6 mEq/L (5.6 mmol/L) (B) Mycophenolate mofetil Chloride 102 mEq/L (102 mmol/L) (C) Prednisone Bicarbonate 26 mEq/L (26 mmol/L) (D) No change in medication is required Urinalysis Specific gravity 1.010; pH 7.5; 1+ blood; 2+ protein; 1+ leukocytes; 1-3 leukocytes/hpf; 3-5 erythrocytes/ Item 108 hpf; fine-needle crystals A 60-year-old woman is evaluated during a follow-up visit Kidney ultrasound shows an 11-cm right kidney and for stage G3 proteinuric chronic kidney disease due to type 2 an 11.8-cm left kidney with normal cortical appearance and diabetes mellitus. Medications are lisinopril and metformin. without hydronephrosis. On physical examination, blood pressure is 137/80 mm Hg, and pulse rate is 83/min; other vital signs are normal. Which of the following is the most likely cause of this The remainder of the examination is normal. patient’s acute kidney injury? Laboratory studies: Hemoglobin A,, 8.3% (A) Acute glomerulonephritis Creatinine 1.3 mg/dL (114.9 umol/L) (B) Acute interstitial nephritis Potassium 4.3 mEq/L (4.3 mmol/L) (C) Acute tubular necrosis Estimated glomerular filtration 45 mL/min/1.73 m? (D) Intratubular obstruction rate Spot urine protein-creatinine 3680 mg/g ratio Item 106 Which of the following is the most appropriate additional A 46-year-old woman is evaluated during a follow-up visit treatment? for hypertension, type 2 diabetes mellitus, and stage G3 chronic kidney disease. She reports no symptoms. Medi- (A) Canagliflozin cations are losartan, amlodipine, metformin, canagliflozin, (B) Glyburide and rosuvastatin. (C) Losartan On physical examination, blood pressure is 124/72 mm (D) Pioglitazone Hg. Other vital signs and the remainder of the examination are unremarkable. (E) Sitagliptin

b= Creatinine 1.6 mg/dL (141.4 umol/L) wn wn (A) Add metolazone Electrolytes: @o i) (B) Administer furosemide by continuous intravenous Sodium 136 mEq/L (136 mmol/L) = infusion Potassium 5.6 mEq/L (5.5 mmol/L) @o = (C) Administer furosemide by intravenous bolus Chloride 104 mEq/L (104 mmol/L) “ (D) Discontinue prednisone; add cyclosporine Bicarbonate 24 mEq/L (24 mmol/L) ry Urine albumin-creatinine ratio 320 mg/g wn oe (E) Hemodialysis with ultrafiltration ECG is normal. The patient is counseled to start a low potassium diet. Item 105 A 33-year-old man is evaluated for acute kidney injury Which of the following is the most appropriate management? 48 hours after being hospitalized for herpes simplex (A) Add hydrochlorothiazide virus encephalitis. Diagnosis was confirmed with poly- (B) Add patiromer merase chain reaction testing of the cerebrospinal fluid. He is being treated with intravenous high-dose acyclo (C) Administer intravenous calcium gluconate vir. Empiric therapy with ceftriaxone plus vancomycin (D) No further treatment was initiated and then discontinued after the results of the cerebrospinal fluid analysis became available. Medical Item 107 history is significant for chronic kidney disease due to hereditary nephritis and hypertension. Outpatient medi A 31-year-old woman seeks preconception counseling. She cations are lisinopril and hydrochlorothiazide, both held has systemic lupus erythematosus and lupus nephritis, both since admission. of which have been stable for the past year; she has had no On physical examination, vital signs are normal. The proteinuria for more than 12 months. She currently feels patient has some difficulty with attention and orientation to well. Medications are mycophenolate mofetil, hydroxychlo- time but is otherwise neurologically intact. The remainder roquine, and low-dose prednisone. of the examination is normal. Physical examination findings, including vital signs, are normal. Current laboratory studies: Creatinine 2.3 mg/dL (203.3 umol/L); Which of the following medications should be baseline: 1.8 mg/dL (159.1 umol/L) discontinued in this patient before conception? Electrolytes: Sodium 137 mEq/L (137 mmol/L) (A) Hydroxychloroquine Potassium 5.6 mEq/L (5.6 mmol/L) (B) Mycophenolate mofetil Chloride 102 mEq/L (102 mmol/L) (C) Prednisone Bicarbonate 26 mEq/L (26 mmol/L) (D) No change in medication is required Urinalysis Specific gravity 1.010; pH 7.5; 1+ blood; 2+ protein; 1+ leukocytes; 1-3 leukocytes/hpf; 3-5 erythrocytes/ Item 108 hpf; fine-needle crystals A 60-year-old woman is evaluated during a follow-up visit Kidney ultrasound shows an 11-cm right kidney and for stage G3 proteinuric chronic kidney disease due to type 2 an 11.8-cm left kidney with normal cortical appearance and diabetes mellitus. Medications are lisinopril and metformin. without hydronephrosis. On physical examination, blood pressure is 137/80 mm Hg, and pulse rate is 83/min; other vital signs are normal. Which of the following is the most likely cause of this The remainder of the examination is normal. patient’s acute kidney injury? Laboratory studies: Hemoglobin A,, 8.3% (A) Acute glomerulonephritis Creatinine 1.3 mg/dL (114.9 umol/L) (B) Acute interstitial nephritis Potassium 4.3 mEq/L (4.3 mmol/L) (C) Acute tubular necrosis Estimated glomerular filtration 45 mL/min/1.73 m? (D) Intratubular obstruction rate Spot urine protein-creatinine 3680 mg/g ratio Item 106 Which of the following is the most appropriate additional A 46-year-old woman is evaluated during a follow-up visit treatment? for hypertension, type 2 diabetes mellitus, and stage G3 chronic kidney disease. She reports no symptoms. Medi- (A) Canagliflozin cations are losartan, amlodipine, metformin, canagliflozin, (B) Glyburide and rosuvastatin. (C) Losartan On physical examination, blood pressure is 124/72 mm (D) Pioglitazone Hg. Other vital signs and the remainder of the examination are unremarkable. (E) Sitagliptin 120

Answers and Critiques C) Item 1 Answer: A Bibliography Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeo- Educational Objective: Diagnose B,-agonist-related stasis. Adv Physiol Educ. 2016;40:480-490. [PMID: 27756725] hypokalemia. The most likely cause of this patient’s hypokalemia is albuterol (Option A). Hypokalemia is defined as a serum potassium Item 2 Answer: C

C) Item 1 Answer: A Bibliography Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeo- Educational Objective: Diagnose B,-agonist-related stasis. Adv Physiol Educ. 2016;40:480-490. [PMID: 27756725] hypokalemia. The most likely cause of this patient’s hypokalemia is albuterol (Option A). Hypokalemia is defined as a serum potassium Item 2 Answer: C level <3.5 mEq/L (3.5 mmol/L). It can be divided into disor- Educational Objective: Prevent contrast-associated ders of internal balance (movement of potassium between nephropathy. w fy s the intracellular and extracellular compartments) and dis- The most appropriate periprocedure measure to prevent = orders of external balance (potassium intake and output). contrast-associated nephropathy (CAN) is to administer intra 9 B.-Agonists such as albuterol that are administered intra- cw) venous 0.9% saline pre- and postprocedure (Option C) for this venously or by inhalation increase the activity of the Na*/ <3 patient undergoing cardiac catheterization. Multiple patient- a K*-ATPase, which drives potassium into cells. This causes a c related risk factors have been associated with CAN. The pri- wn transient decline in the extracellular potassium concentra- ross

level <3.5 mEq/L (3.5 mmol/L). It can be divided into disor- Educational Objective: Prevent contrast-associated ders of internal balance (movement of potassium between nephropathy. w fy s the intracellular and extracellular compartments) and dis- The most appropriate periprocedure measure to prevent = orders of external balance (potassium intake and output). contrast-associated nephropathy (CAN) is to administer intra 9 B.-Agonists such as albuterol that are administered intra- cw) venous 0.9% saline pre- and postprocedure (Option C) for this venously or by inhalation increase the activity of the Na*/ <3 patient undergoing cardiac catheterization. Multiple patient- a K*-ATPase, which drives potassium into cells. This causes a c related risk factors have been associated with CAN. The pri- wn transient decline in the extracellular potassium concentra- ross mary risk factor is a reduced estimated glomerular filtration o tion. The decline in serum potassium is dose dependent and = rate (eGFR). Some studies find an added risk of CAN from dia- Ww related to the potency of the drug, averaging approximately = betes mellitus. Well-established additional risk factors include <= 0.5 mEq/L (0.5 mmol/L) but can be much greater. In patients nephrotoxic agents and exposures, hypotension, hypovolemia, with underlying heart disease, the rapid decline in serum albuminuria, and impaired kidney perfusion (e.g., as occurs in potassium can cause fatal arrhythmias. When significant heart failure). Although multiple myeloma has historically been hypokalemia is secondary to acute transcellular shifts, such considered a risk factor for CAN, this is not supported by more as in this case, total body potassium is normal and excessive recent literature. A 2020 guideline from the American College potassium replacement may cause rebound hyperkalemia. of Radiology and the National Kidney Foundation recommends Similar to B,-agonists, insulin increases Na*/K*-ATPase that the risk for CAN be determined primarily by using the activity and will acutely lower the extracellular potassium chronic kidney disease stage and associated eGFR measure- concentration. This effect of insulin on potassium homeo- ment. Patients at highest risk for CAN include those with recent stasis is separate from its effect on glucose metabolism. In acute kidney injury and those with an eGFR <30 mL/min/ this patient, however, it is unlikely that his hyperglycemia 1.73 m?. Prophylaxis with intravenous 0.9% saline pre- and with a serum glucose level of 124 mg/dL (6.9 mmol/L) is high postprocedure is indicated for patients not undergoing dialysis enough (Option B) to stimulate significant insulin release to who have an eGFR <30 mL/min/1.73 m? or acute kidney injury. cause hypokalemia. In individual high-risk circumstances, prophylaxis may be con- Blockage of the cellular potassium channel by the diva- sidered in patients with eGFR of 30 to 44 mL/min/1.73 m?2 at the lent cation barium can cause acute decreases in serum potas- discretion of the ordering clinician. Prophylaxis is not indicated sium. Although magnesium is a divalent cation, it does not for patients with stable eGFR 245 mL/min/1.73 m2. The pres- affect the potassium channel in cell membranes, and thus ence of a solitary kidney should not independently influence hypermagnesemia (Option C) cannot cause hypokalemia. decision-making regarding the risk for CAN. Although prednisone (Option D) has mineralocorticoid Renal replacement therapy should neither be initiated activity, any mineralocorticoid increase in potassium excre nor have a schedule adjustment solely based on contrast tion would not occur rapidly and would therefore not explain media administration. Postprocedure initiation of hemodial. this patient’s hypokalemia. In addition, hyperaldosteronism ysis (Option A) directed at removal of contrast from the blood is associated with hypertension and a metabolic alkalosis. has been attempted in a few small studies with mixed results. Respiratory disturbances have minimal effect on potas- Neither infusion of sodium bicarbonate pre- and sium distribution, and thus respiratory alkalosis (Option E) postprocedure (Option B) nor use of oral N-acetylcysteine would not be expected to cause a significant decrease in (Option D) is recommended to prevent CAN due to a lack of potassium in this patient. consistent evidence demonstrating efficacy.

mary risk factor is a reduced estimated glomerular filtration o tion. The decline in serum potassium is dose dependent and = rate (eGFR). Some studies find an added risk of CAN from dia- Ww related to the potency of the drug, averaging approximately = betes mellitus. Well-established additional risk factors include <= 0.5 mEq/L (0.5 mmol/L) but can be much greater. In patients nephrotoxic agents and exposures, hypotension, hypovolemia, with underlying heart disease, the rapid decline in serum albuminuria, and impaired kidney perfusion (e.g., as occurs in potassium can cause fatal arrhythmias. When significant heart failure). Although multiple myeloma has historically been hypokalemia is secondary to acute transcellular shifts, such considered a risk factor for CAN, this is not supported by more as in this case, total body potassium is normal and excessive recent literature. A 2020 guideline from the American College potassium replacement may cause rebound hyperkalemia. of Radiology and the National Kidney Foundation recommends Similar to B,-agonists, insulin increases Na*/K*-ATPase that the risk for CAN be determined primarily by using the activity and will acutely lower the extracellular potassium chronic kidney disease stage and associated eGFR measure- concentration. This effect of insulin on potassium homeo- ment. Patients at highest risk for CAN include those with recent stasis is separate from its effect on glucose metabolism. In acute kidney injury and those with an eGFR <30 mL/min/ this patient, however, it is unlikely that his hyperglycemia 1.73 m?. Prophylaxis with intravenous 0.9% saline pre- and with a serum glucose level of 124 mg/dL (6.9 mmol/L) is high postprocedure is indicated for patients not undergoing dialysis enough (Option B) to stimulate significant insulin release to who have an eGFR <30 mL/min/1.73 m? or acute kidney injury. cause hypokalemia. In individual high-risk circumstances, prophylaxis may be con- Blockage of the cellular potassium channel by the diva- sidered in patients with eGFR of 30 to 44 mL/min/1.73 m?2 at the lent cation barium can cause acute decreases in serum potas- discretion of the ordering clinician. Prophylaxis is not indicated sium. Although magnesium is a divalent cation, it does not for patients with stable eGFR 245 mL/min/1.73 m2. The pres- affect the potassium channel in cell membranes, and thus ence of a solitary kidney should not independently influence hypermagnesemia (Option C) cannot cause hypokalemia. decision-making regarding the risk for CAN. Although prednisone (Option D) has mineralocorticoid Renal replacement therapy should neither be initiated activity, any mineralocorticoid increase in potassium excre nor have a schedule adjustment solely based on contrast tion would not occur rapidly and would therefore not explain media administration. Postprocedure initiation of hemodial. this patient’s hypokalemia. In addition, hyperaldosteronism ysis (Option A) directed at removal of contrast from the blood is associated with hypertension and a metabolic alkalosis. has been attempted in a few small studies with mixed results. Respiratory disturbances have minimal effect on potas- Neither infusion of sodium bicarbonate pre- and sium distribution, and thus respiratory alkalosis (Option E) postprocedure (Option B) nor use of oral N-acetylcysteine would not be expected to cause a significant decrease in (Option D) is recommended to prevent CAN due to a lack of potassium in this patient. consistent evidence demonstrating efficacy. ¢ B,-Agonists can cause hypokalemia by facilitating ¢ Contrast-associated nephropathy prophylaxis with intercellular shifts of potassium. intravenous 0.9% saline pre- and postprocedure is indi- e When hypokalemia is secondary to acute transcellular cated for patients who have an estimated glomerular fil- shifts, total body potassium is normal and potassium tration rate <30 mL/min/1.73 m? or acute kidney injury. replacement may cause rebound hyperkalemia. (Continued)

¢ B,-Agonists can cause hypokalemia by facilitating ¢ Contrast-associated nephropathy prophylaxis with intercellular shifts of potassium. intravenous 0.9% saline pre- and postprocedure is indi- e When hypokalemia is secondary to acute transcellular cated for patients who have an estimated glomerular fil- shifts, total body potassium is normal and potassium tration rate <30 mL/min/1.73 m? or acute kidney injury. replacement may cause rebound hyperkalemia. (Continued) 121

pe: ba eli ¢ Contrast-associated nephropathy prophylaxis is not e The initial step in the management of newly diag- indicated for patients with a stable estimated glomer- nosed membranous nephropathy (MN) is to evaluate ular filtration rate >45 mL/min/1.73 m?. for secondary forms of the disease, and cancer screen- ing is particularly important in evaluating for second- Bibliography ary forms of MN in patients >65 years of age. Davenport MS, Perazella MA, Yee J, et al. Use of intravenous iodinated con- ¢ Testing for phospholipase A2 receptor (PLA2R) antigen trast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney Foundation. is used to help distinguish primary (PLA2R antigen- Radiology 2020;294:660. doi.org/10.1148/radiol.2019192094 positive) from secondary (PLA2R antigen-negative) forms of membranous nephropathy.

¢ Contrast-associated nephropathy prophylaxis is not e The initial step in the management of newly diag- indicated for patients with a stable estimated glomer- nosed membranous nephropathy (MN) is to evaluate ular filtration rate >45 mL/min/1.73 m?. for secondary forms of the disease, and cancer screen- ing is particularly important in evaluating for second- Bibliography ary forms of MN in patients >65 years of age. Davenport MS, Perazella MA, Yee J, et al. Use of intravenous iodinated con- ¢ Testing for phospholipase A2 receptor (PLA2R) antigen trast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney Foundation. is used to help distinguish primary (PLA2R antigen- Radiology 2020;294:660. doi.org/10.1148/radiol.2019192094 positive) from secondary (PLA2R antigen-negative) forms of membranous nephropathy. Item 3 Answer: C P= Bibliography = Educational Objective: Screen for malignancy in an wr Khairallah P, Bomback AS. Membranous nephropathy and cancer in the era of = older patient with membranous nephropathy. PLA,R testing. JOnco-Nephrol. 2018;2:50-55. doi/10.1177/2399369318816333 oO = w A noncontrast CT of the chest (Option C) should be per- ts) 1] formed to screen for lung cancer in this patient newly Qa. Item 4 Answer: C diagnosed with phospholipase A2 receptor (PLA2R)- a =e negative membranous nephropathy (MN) and a history Educational Objective: Manage a patient following ini- = of heavy tobacco use. Testing for PLA2R antigen is used tiation of a renin-angiotensin system inhibitor. & = to help distinguish primary from secondary forms of MN. J The most appropriate treatment for this patient is to discon- wn This distinction is crucial because secondary (PLA2R tinue lisinopril and add furosemide (Option C). Treatment of antigen-negative) forms are expected to remit if the hypertension with a renin-angiotensin system inhibitor, such underlying systemic disease responsible for the lesion is as an ACE inhibitor (e.g., lisinopril) or an angiotensin receptor successfully treated. Therefore, age- and sex-appropriate blocker (ARB) (e.g., losartan), is indicated in patients with stage cancer screening is recommended for all patients at the G3 chronic kidney disease (CKD) or higher or for those with time of diagnosis, even those with PLA2R positivity. stage G1 or G2 CKD with albuminuria (urine albumin-creatinine Thus, the initial step in management of newly diag- ratio >300 mg/g). However, kidney function and serum potas- nosed MN is to evaluate for secondary forms of the dis- sium levels should be reassessed 2 to 3 weeks after initiation ofan ease, which account for approximately 25% of MN cases ACE inhibitor or ARB. A 25% to 30% increase in serum creatinine and include lupus-, hepatitis-, drug-, and malignancy- is acceptable, but the dose may need to be lowered or the medi- associated forms of MN. Cancer screening is particularly cation discontinued if'a more severe decline in kidney function is important in evaluating for secondary forms of MN in observed, such as in this patient. A decrease of the glomerular fil- patients >65 years of age. Up to 25% of such patients will tration rate of this magnitude is usually the result of renovascular have a malignancy discovered within 1 year of diagno- hypertension. In patients with significant hyperkalemia, a loop sis. This 69-year-old man with a 45-pack-year history diuretic such as furosemide can be added to promote kaliuresis. of smoking has not undergone risk factor-appropriate Continuing lisinopril, with or without the addition cancer screening, which would include a noncontrast of furosemide (Options A, B), or replacing lisinopril with CT of the chest. losartan (Option D), places the patient at increased risk for Renal vein thrombosis is found in up to 20% of patients progressive kidney injury and hyperkalemia. However, dis- with MN. Doppler ultrasonography screening for renal vein continuation of lisinopril in this case is a temporary solution. thrombosis (Option A) is reserved for when acute kidney This patient’s laboratory tests can be repeated in 2 to 3 weeks injury, flank pain, and/or gross hematuria raise suspicion for after the discontinuation of lisinopril and addition of furo- this complication. semide. If the laboratory tests have normalized, reinitiation MN is associated with a higher risk for clotting when of lisinopril at a lower dose can be considered with careful serum albumin is <2.8 g/dL (28 g/L); this patient’s serum monitoring of serum creatinine and potassium levels. albumin is 2.9 g/dL (29 g/L). The symmetric lower extremity edema in this patient is more consistent with the nephrotic syndrome than a lower extremity clot; therefore, Dop- e In patients with chronic kidney disease, kidney func- pler ultrasonography of his legs (Option B) would not be tion and serum potassium levels should be reassessed required. 2 to 3 weeks after initiation of an ACE inhibitor or Random (spot) urine protein-creatinine ratio (Option angiotensin receptor blocker. D), particularly when collected on first morning void, can ¢ Following initiation of an ACE inhibitor or angiotensin serve as a surrogate for 24-hour urine protein quantifica- receptor blocker, a >30% increase in serum creatinine tion. This test is unnecessary in this case, as the more accu- levels necessitates decreasing the dose of or discontin- rate quantification of proteinuria via 24-hour urine protein uing these agents. excretion has already been performed.

Item 3 Answer: C P= Bibliography = Educational Objective: Screen for malignancy in an wr Khairallah P, Bomback AS. Membranous nephropathy and cancer in the era of = older patient with membranous nephropathy. PLA,R testing. JOnco-Nephrol. 2018;2:50-55. doi/10.1177/2399369318816333 oO = w A noncontrast CT of the chest (Option C) should be per- ts) 1] formed to screen for lung cancer in this patient newly Qa. Item 4 Answer: C diagnosed with phospholipase A2 receptor (PLA2R)- a =e negative membranous nephropathy (MN) and a history Educational Objective: Manage a patient following ini- = of heavy tobacco use. Testing for PLA2R antigen is used tiation of a renin-angiotensin system inhibitor. & = to help distinguish primary from secondary forms of MN. J The most appropriate treatment for this patient is to discon- wn This distinction is crucial because secondary (PLA2R tinue lisinopril and add furosemide (Option C). Treatment of antigen-negative) forms are expected to remit if the hypertension with a renin-angiotensin system inhibitor, such underlying systemic disease responsible for the lesion is as an ACE inhibitor (e.g., lisinopril) or an angiotensin receptor successfully treated. Therefore, age- and sex-appropriate blocker (ARB) (e.g., losartan), is indicated in patients with stage cancer screening is recommended for all patients at the G3 chronic kidney disease (CKD) or higher or for those with time of diagnosis, even those with PLA2R positivity. stage G1 or G2 CKD with albuminuria (urine albumin-creatinine Thus, the initial step in management of newly diag- ratio >300 mg/g). However, kidney function and serum potas- nosed MN is to evaluate for secondary forms of the dis- sium levels should be reassessed 2 to 3 weeks after initiation ofan ease, which account for approximately 25% of MN cases ACE inhibitor or ARB. A 25% to 30% increase in serum creatinine and include lupus-, hepatitis-, drug-, and malignancy- is acceptable, but the dose may need to be lowered or the medi- associated forms of MN. Cancer screening is particularly cation discontinued if'a more severe decline in kidney function is important in evaluating for secondary forms of MN in observed, such as in this patient. A decrease of the glomerular fil- patients >65 years of age. Up to 25% of such patients will tration rate of this magnitude is usually the result of renovascular have a malignancy discovered within 1 year of diagno- hypertension. In patients with significant hyperkalemia, a loop sis. This 69-year-old man with a 45-pack-year history diuretic such as furosemide can be added to promote kaliuresis. of smoking has not undergone risk factor-appropriate Continuing lisinopril, with or without the addition cancer screening, which would include a noncontrast of furosemide (Options A, B), or replacing lisinopril with CT of the chest. losartan (Option D), places the patient at increased risk for Renal vein thrombosis is found in up to 20% of patients progressive kidney injury and hyperkalemia. However, dis- with MN. Doppler ultrasonography screening for renal vein continuation of lisinopril in this case is a temporary solution. thrombosis (Option A) is reserved for when acute kidney This patient’s laboratory tests can be repeated in 2 to 3 weeks injury, flank pain, and/or gross hematuria raise suspicion for after the discontinuation of lisinopril and addition of furo- this complication. semide. If the laboratory tests have normalized, reinitiation MN is associated with a higher risk for clotting when of lisinopril at a lower dose can be considered with careful serum albumin is <2.8 g/dL (28 g/L); this patient’s serum monitoring of serum creatinine and potassium levels. albumin is 2.9 g/dL (29 g/L). The symmetric lower extremity edema in this patient is more consistent with the nephrotic syndrome than a lower extremity clot; therefore, Dop- e In patients with chronic kidney disease, kidney func- pler ultrasonography of his legs (Option B) would not be tion and serum potassium levels should be reassessed required. 2 to 3 weeks after initiation of an ACE inhibitor or Random (spot) urine protein-creatinine ratio (Option angiotensin receptor blocker. D), particularly when collected on first morning void, can ¢ Following initiation of an ACE inhibitor or angiotensin serve as a surrogate for 24-hour urine protein quantifica- receptor blocker, a >30% increase in serum creatinine tion. This test is unnecessary in this case, as the more accu- levels necessitates decreasing the dose of or discontin- rate quantification of proteinuria via 24-hour urine protein uing these agents. excretion has already been performed. 122

Bibliography Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, ¢ Screening for renal cell carcinoma in patients with detection, evaluation, and management of high blood pressure in adults: end-stage kidney disease and acquired cystic kidney a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. disease may be reasonable in patients with a longer 2018:71:e127-e248. [PMID: 29146535] doi: 10.1016 /j.jacc.2017.11.006 life expectancy. Item 5 Answer: A Bibliography Tsuzuki T, Iwata H, Murase Y, et al. Renal tumors in end-stage renal disease: Educational Objective: Screen for renal cell carcinoma a comprehensive review. Int J Urol. 2018;25:780-786. [PMID: 30066367] in a patient with acquired cystic kidney disease. doi:10.1111/iju.13759

Item 5 Answer: A Bibliography Tsuzuki T, Iwata H, Murase Y, et al. Renal tumors in end-stage renal disease: Educational Objective: Screen for renal cell carcinoma a comprehensive review. Int J Urol. 2018;25:780-786. [PMID: 30066367] in a patient with acquired cystic kidney disease. doi:10.1111/iju.13759 The most appropriate management of this patient’s acquired kidney cysts is annual kidney ultrasonography (Option A). Patients with end-stage kidney disease (ESKD) are at increased Item 6 Answer: A wn a 3 risk for renal cell carcinoma compared with the general popu- Educational Objective: Treat myeloma cast nephropathy. = lation. Acquired cystic changes of the kidney are common in The most appropriate treatment is chemotherapy (Option A). = patients with severe chronic kidney disease (CKD) and ESKD cs) This patient presents with acute kidney injury (AKI), ane- sc and are at risk for malignant transformation. Risk factors e mia, hypercalcemia, and a biopsy confirming the presence os] for acquired cystic kidney disease include longer duration

The most appropriate management of this patient’s acquired kidney cysts is annual kidney ultrasonography (Option A). Patients with end-stage kidney disease (ESKD) are at increased Item 6 Answer: A wn a 3 risk for renal cell carcinoma compared with the general popu- Educational Objective: Treat myeloma cast nephropathy. = lation. Acquired cystic changes of the kidney are common in The most appropriate treatment is chemotherapy (Option A). = patients with severe chronic kidney disease (CKD) and ESKD cs) This patient presents with acute kidney injury (AKI), ane- sc and are at risk for malignant transformation. Risk factors e mia, hypercalcemia, and a biopsy confirming the presence os] for acquired cystic kidney disease include longer duration 5 of myeloma cast nephropathy. Myeloma cast nephropathy of ESKD and dialysis and male sex. For patients with ESKD is caused by the interaction and aggregation of filtered free and acquired kidney cysts, decisions about screening must be > wa light chains and Tamm-Horsfall protein causing intratubular individualized based on the competing issues of risk for renal = obstruction and damage. Rapid lowering of free light chains <= cell carcinoma versus a shortened overall life expectancy. This with bortezomib-based chemotherapy with high-dose dexa- young patient is a kidney transplant candidate with extended methasone correlates with kidney recovery and is more effec- life expectancy. His kidney ultrasound confirms the presence tive than plasmapheresis or hemodialysis. of acquired cysts, a few of which are complex with internal In this patient with preserved urine output, hemodial- septations; however, there is no evidence of malignant change ysis (Option B) with either a high-cutoff or regular dialyzer with no solid components or neovascularization. This patient would not be recommended. Extended high-cutoff hemodi- should have annual ultrasonography of the kidneys to mon- alysis uses a high-cutoff dialyzer with very large membrane itor for malignant conversion and undergo nephrectomy if a pores and high permeability to immunoglobulin light chains suspicious mass develops. to remove free light chains. This high-cutoff hemodialysis Preemptive nephrectomy (Option B) is an invasive has proven better than conventional hemodialysis in lower- intervention that would put this patient at risk for surgical ing light chain burden, but in a randomized trial of patients complications with no clear benefit; he has no evidence of with myeloma cast nephropathy treated with a bortezomib- renal cell carcinoma or other indications for nephrectomy, based chemotherapy regimen, the use of high-cutoff hemo- such as recurrent infections related to the kidney. dialysis did not result in improved kidney survival compared Tolvaptan (Option C) has been FDA approved for treat- with conventional hemodialysis. These data suggest that ment of patients with autosomal dominant polycystic kidney the use of chemotherapy is the most important factor in disease. However, there is no role for tolvaptan in patients reduction of light chain burden. Fluid overload, hyperkale- with acquired kidney cysts. mia, and uremia remain indications for hemodialysis in all For older patients with ESKD and those who are not patients with AKI. transplant candidates, screening is not recommended Hospice referral (Option C) is premature for this (Option D), even in the presence of known acquired cys- patient. Nearly 50% of all patients with multiple myeloma tic kidney disease. The American Society of Nephrology’s develop kidney disease, most commonly AKI caused by Choosing Wisely Campaign recommends not screening for cast nephropathy, and this complication does lead to malignancy in patients with reduced life expectancy. How- reduced 1-year survival rates. However, advances in che- ever, because of the increased risk for renal cell carcinoma in motherapy regimens are improving both mortality rates this patient population, development of symptoms or signs and kidney survival rates, and this patient with a normal consistent with renal cell carcinoma should be investigated. functional status and no comorbidities would benefit from For example, spontaneous improvement in hemoglobin is chemotherapy. suspicious for renal cell carcinoma-related erythropoietin Small trials initially showed that therapeutic plas- production. mapheresis (Option D) improved renal outcomes in myeloma cast nephropathy, but a large randomized trial

5 of myeloma cast nephropathy. Myeloma cast nephropathy of ESKD and dialysis and male sex. For patients with ESKD is caused by the interaction and aggregation of filtered free and acquired kidney cysts, decisions about screening must be > wa light chains and Tamm-Horsfall protein causing intratubular individualized based on the competing issues of risk for renal = obstruction and damage. Rapid lowering of free light chains <= cell carcinoma versus a shortened overall life expectancy. This with bortezomib-based chemotherapy with high-dose dexa- young patient is a kidney transplant candidate with extended methasone correlates with kidney recovery and is more effec- life expectancy. His kidney ultrasound confirms the presence tive than plasmapheresis or hemodialysis. of acquired cysts, a few of which are complex with internal In this patient with preserved urine output, hemodial- septations; however, there is no evidence of malignant change ysis (Option B) with either a high-cutoff or regular dialyzer with no solid components or neovascularization. This patient would not be recommended. Extended high-cutoff hemodi- should have annual ultrasonography of the kidneys to mon- alysis uses a high-cutoff dialyzer with very large membrane itor for malignant conversion and undergo nephrectomy if a pores and high permeability to immunoglobulin light chains suspicious mass develops. to remove free light chains. This high-cutoff hemodialysis Preemptive nephrectomy (Option B) is an invasive has proven better than conventional hemodialysis in lower- intervention that would put this patient at risk for surgical ing light chain burden, but in a randomized trial of patients complications with no clear benefit; he has no evidence of with myeloma cast nephropathy treated with a bortezomib- renal cell carcinoma or other indications for nephrectomy, based chemotherapy regimen, the use of high-cutoff hemo- such as recurrent infections related to the kidney. dialysis did not result in improved kidney survival compared Tolvaptan (Option C) has been FDA approved for treat- with conventional hemodialysis. These data suggest that ment of patients with autosomal dominant polycystic kidney the use of chemotherapy is the most important factor in disease. However, there is no role for tolvaptan in patients reduction of light chain burden. Fluid overload, hyperkale- with acquired kidney cysts. mia, and uremia remain indications for hemodialysis in all For older patients with ESKD and those who are not patients with AKI. transplant candidates, screening is not recommended Hospice referral (Option C) is premature for this (Option D), even in the presence of known acquired cys- patient. Nearly 50% of all patients with multiple myeloma tic kidney disease. The American Society of Nephrology’s develop kidney disease, most commonly AKI caused by Choosing Wisely Campaign recommends not screening for cast nephropathy, and this complication does lead to malignancy in patients with reduced life expectancy. How- reduced 1-year survival rates. However, advances in che- ever, because of the increased risk for renal cell carcinoma in motherapy regimens are improving both mortality rates this patient population, development of symptoms or signs and kidney survival rates, and this patient with a normal consistent with renal cell carcinoma should be investigated. functional status and no comorbidities would benefit from For example, spontaneous improvement in hemoglobin is chemotherapy. suspicious for renal cell carcinoma-related erythropoietin Small trials initially showed that therapeutic plas- production. mapheresis (Option D) improved renal outcomes in myeloma cast nephropathy, but a large randomized trial e Patients with end-stage kidney disease are at of therapeutic plasmapheresis failed to show benefit. If used, plasmapheresis is combined with chemotherapy to increased risk for renal cell carcinoma. reduce the rate of light chain production rather than as (Continued) monotherapy.

e Patients with end-stage kidney disease are at of therapeutic plasmapheresis failed to show benefit. If used, plasmapheresis is combined with chemotherapy to increased risk for renal cell carcinoma. reduce the rate of light chain production rather than as (Continued) monotherapy. 123

Answers and Critiques e Initiation of chemotherapy is the most appropriate e Patients with the nephrotic syndrome and hypoalbu- treatment for myeloma cast nephropathy and is aimed minemia are at increased risk for venous thromboem- at reducing the concentration of free light chains. bolism (VTE); VTE is most often seen in patients with membranous nephropathy. Bibliography e Prophylactic anticoagulation of asymptomatic Finkel KW, Cohen EP, Shirali A, et al; American Society of Nephrology Onco- patients with the nephrotic syndrome and hypoalbu- Nephrology Forum. Paraprotein-related kidney disease: evaluation and treatment of myeloma cast nephropathy. Clin J Am Soc Nephrol. 2016; minemia is controversial. 11:2273-2279. [PMID: 27526708]

e Initiation of chemotherapy is the most appropriate e Patients with the nephrotic syndrome and hypoalbu- treatment for myeloma cast nephropathy and is aimed minemia are at increased risk for venous thromboem- at reducing the concentration of free light chains. bolism (VTE); VTE is most often seen in patients with membranous nephropathy. Bibliography e Prophylactic anticoagulation of asymptomatic Finkel KW, Cohen EP, Shirali A, et al; American Society of Nephrology Onco- patients with the nephrotic syndrome and hypoalbu- Nephrology Forum. Paraprotein-related kidney disease: evaluation and treatment of myeloma cast nephropathy. Clin J Am Soc Nephrol. 2016; minemia is controversial. 11:2273-2279. [PMID: 27526708] Bibliography Gyamlani G, Molnar MZ, Lu JL, et al. Association of serum albumin level and Item 7 Answer: D venous thromboembolic events in a large cohort of patients with = _ Educational Objective: Identify hypercoagulability as a nephrotic syndrome. Nephrol Dial Transplant. 2017;32:157-164. [PMID: wn 28391310] doi:10.1093/ndt/gfw227 = complication of the nephrotic syndrome. © —~ wn The most likely complication to develop in this patient & = during the next 12 months is venous thromboembolism ltem 8 Answer: A Qa. (VTE) (Option D). The nephrotic syndrome is a hyperco- a Educational Objective: Evaluate progressive kidney = agulable state due to urinary losses of anticoagulant pro- a. disease. 2 teins (antithrombin III, protein S) and fibrinolytics as well © o as hepatic overproduction of procoagulant proteins (fac- The most appropriate management is kidney biopsy (Option wn tor V, factor VIII, fibrinogen). A very low serum albumin A) for this patient with a significant decline in kidney func- level seems to be a surrogate measure for abnormalities in tion. In addition, this patient has unexplained moderately antithrombin and fibrinogen. As a result, patients with the increased albuminuria and an increase in echogenicity on nephrotic syndrome are at increased risk for lower extrem- kidney ultrasound, suggesting a chronic condition. Clinical ity, pulmonary, and renal vein thrombosis. Clots are most and laboratory features are often insufficient for definitive often seen in patients with membranous nephropathy, such diagnosis of kidney disease. Therefore, kidney biopsy may be as this patient, in which VTE risk appears to begin at a serum essential for diagnosis and management. Indications include albumin level <2.8 g/dL (28 g/L) and increases proportion- glomerular hematuria, severely increased albuminuria, acute ately with declining albumin levels. Therefore, any patient or chronic kidney disease of unclear cause, and kidney trans- with nephrotic-range proteinuria and significant hypoalbu- plant dysfunction or monitoring. In this case, the patient has minemia (typically <2.5 g/dL [25 g/L]) should be considered an elevated serum creatinine level with albuminuria and pos- at risk. Most VTE events occur in the first 6 months after a sible chronic kidney disease without a clear cause. Although diagnosis of the nephrotic syndrome is made. Prophylactic further urine and serologic testing will be performed to guide anticoagulation of asymptomatic patients with the nephrotic diagnosis, a kidney biopsy will provide definitive diagnosis. syndrome and hypoalbuminemia is controversial, and no The patient has moderately increased albuminuria randomized clinical trials are available to help guide clinical (albumin-creatinine ratio of 30-300 mg/g). The urine decision-making. protein-creatinine ratio will be greater than the urine Diabetes mellitus (Option A) is the most common cause albumin-creatinine ratio due to the presence of nonalbumin of the nephrotic syndrome. Other causes of the nephrotic protein and therefore will be in the pathologic range. There- syndrome do not predispose the development of diabetes fore, random urine protein-creatinine ratio (Option B) will mellitus, independent of the role that glucocorticoid therapy not add new information in this case. may play in predisposing a patient to hyperglycemia. Because the patient has a significant loss of kidney func- Approximately one third of patients with membranous tion, a reassessment of serum creatinine in 3 months (Option nephropathy achieve spontaneous remission in the first year C) would not be appropriate and would result in potentially following diagnosis. Of those who do not achieve remission, harmful delay in the diagnosis of a treatable disease. 75% will respond to immunosuppression with glucocorti- Discontinuation of lisinopril for hydrochlorothiazide coids plus alkylator agents, calcineurin inhibitors, or ritux- (Option D) is not indicated. Due to preferential dilation of imab. Progression to end-stage kidney disease (Option B) the efferent arteriole, the ACE inhibitor lisinopril may reduce requiring dialysis is unlikely, especially in the first year of glomerular filtration rate and increase serum creatinine; the diagnosis. however, this change in serum creatinine will occur within Pulmonary hemorrhage (Option C) is a complica- days of drug initiation and then will stabilize. In this case, tion associated with glomerulonephritis caused by anti- the serum creatinine increased without a change in dose, glomerular basement membrane antibody disease or suggesting that lisinopril is not the cause of the rising serum possibly with ANCA-associated glomerulonephritis; creatinine and will not be resolved by discontinuing the however, it is not expected in a patient with membranous drug. In addition, treatment with lisinopril cannot account nephropathy. for the presence of albuminuria.

Bibliography Gyamlani G, Molnar MZ, Lu JL, et al. Association of serum albumin level and Item 7 Answer: D venous thromboembolic events in a large cohort of patients with = _ Educational Objective: Identify hypercoagulability as a nephrotic syndrome. Nephrol Dial Transplant. 2017;32:157-164. [PMID: wn 28391310] doi:10.1093/ndt/gfw227 = complication of the nephrotic syndrome. © —~ wn The most likely complication to develop in this patient & = during the next 12 months is venous thromboembolism ltem 8 Answer: A Qa. (VTE) (Option D). The nephrotic syndrome is a hyperco- a Educational Objective: Evaluate progressive kidney = agulable state due to urinary losses of anticoagulant pro- a. disease. 2 teins (antithrombin III, protein S) and fibrinolytics as well © o as hepatic overproduction of procoagulant proteins (fac- The most appropriate management is kidney biopsy (Option wn tor V, factor VIII, fibrinogen). A very low serum albumin A) for this patient with a significant decline in kidney func- level seems to be a surrogate measure for abnormalities in tion. In addition, this patient has unexplained moderately antithrombin and fibrinogen. As a result, patients with the increased albuminuria and an increase in echogenicity on nephrotic syndrome are at increased risk for lower extrem- kidney ultrasound, suggesting a chronic condition. Clinical ity, pulmonary, and renal vein thrombosis. Clots are most and laboratory features are often insufficient for definitive often seen in patients with membranous nephropathy, such diagnosis of kidney disease. Therefore, kidney biopsy may be as this patient, in which VTE risk appears to begin at a serum essential for diagnosis and management. Indications include albumin level <2.8 g/dL (28 g/L) and increases proportion- glomerular hematuria, severely increased albuminuria, acute ately with declining albumin levels. Therefore, any patient or chronic kidney disease of unclear cause, and kidney trans- with nephrotic-range proteinuria and significant hypoalbu- plant dysfunction or monitoring. In this case, the patient has minemia (typically <2.5 g/dL [25 g/L]) should be considered an elevated serum creatinine level with albuminuria and pos- at risk. Most VTE events occur in the first 6 months after a sible chronic kidney disease without a clear cause. Although diagnosis of the nephrotic syndrome is made. Prophylactic further urine and serologic testing will be performed to guide anticoagulation of asymptomatic patients with the nephrotic diagnosis, a kidney biopsy will provide definitive diagnosis. syndrome and hypoalbuminemia is controversial, and no The patient has moderately increased albuminuria randomized clinical trials are available to help guide clinical (albumin-creatinine ratio of 30-300 mg/g). The urine decision-making. protein-creatinine ratio will be greater than the urine Diabetes mellitus (Option A) is the most common cause albumin-creatinine ratio due to the presence of nonalbumin of the nephrotic syndrome. Other causes of the nephrotic protein and therefore will be in the pathologic range. There- syndrome do not predispose the development of diabetes fore, random urine protein-creatinine ratio (Option B) will mellitus, independent of the role that glucocorticoid therapy not add new information in this case. may play in predisposing a patient to hyperglycemia. Because the patient has a significant loss of kidney func- Approximately one third of patients with membranous tion, a reassessment of serum creatinine in 3 months (Option nephropathy achieve spontaneous remission in the first year C) would not be appropriate and would result in potentially following diagnosis. Of those who do not achieve remission, harmful delay in the diagnosis of a treatable disease. 75% will respond to immunosuppression with glucocorti- Discontinuation of lisinopril for hydrochlorothiazide coids plus alkylator agents, calcineurin inhibitors, or ritux- (Option D) is not indicated. Due to preferential dilation of imab. Progression to end-stage kidney disease (Option B) the efferent arteriole, the ACE inhibitor lisinopril may reduce requiring dialysis is unlikely, especially in the first year of glomerular filtration rate and increase serum creatinine; the diagnosis. however, this change in serum creatinine will occur within Pulmonary hemorrhage (Option C) is a complica- days of drug initiation and then will stabilize. In this case, tion associated with glomerulonephritis caused by anti- the serum creatinine increased without a change in dose, glomerular basement membrane antibody disease or suggesting that lisinopril is not the cause of the rising serum possibly with ANCA-associated glomerulonephritis; creatinine and will not be resolved by discontinuing the however, it is not expected in a patient with membranous drug. In addition, treatment with lisinopril cannot account nephropathy. for the presence of albuminuria. 124

Answers and Critiques e Indications for kidney biopsy include glomerular e Severe preeclampsia is identified by persistent systolic hematuria, severely increased albuminuria, acute or blood pressure >160 mm Hg or diastolic blood pressure chronic kidney disease of unclear cause, and kidney >110 mm Hg and end-organ damage. transplant dysfunction or monitoring. e Initial therapy for severe preeclampsia is magnesium, antihypertensive medication, and immediate delivery Bibliography of the fetus. Luciano RL, Moeckel GW. Update on the native kidney biopsy: core curricu- lum 2019. Am J Kidney Dis. 2019;73:404-415. [PMID: 30661724] doi:10.1053/j.ajkd.2018.10.011 Bibliography ACOG committee opinion no. 767 summary: emergent therapy for acute- onset, severe hypertension during pregnancy and the postpartum period [editorial]. Obstet Gynecol. 2019;133:409-412. [PMID: 30681541] doi:10. 1097/AOG.0000000000003082 Ww Item 9 Answer: A ch 4 Educational Objective: Treat severe preeclampsia. = = The most appropriate treatment is to continue current Item 10 Answer: A oO therapy (Option A). Severe preeclampsia is identified by os Educational Objective: Treat gastroesophageal reflux <= persistent systolic blood pressure (BP) >160 mm Hg or dia- ) disease in a patient with advanced chronic kidney disease. w stolic BP >110 mm Hg and end-organ damage. The HELLP od o (hemolysis, elevated liver enzymes, low platelets) syndrome The most appropriate additional therapy is famotidine = w may represent a severe form of preeclampsia. In the HELLP (Option A). This patient has stage G4 chronic kidney disease = 4 syndrome, the hemolytic anemia, thrombocytopenia, and (CKD) and symptoms of his gastroesophageal reflux disease liver dysfunction are more prominent, whereas severe pre (GERD). In patients with CKD, the nephrotoxic risk of med- eclampsia has greater BP elevations. This patient has severe ication or treatment used for comorbid medical conditions preeclampsia with features of the HELLP syndrome. The must be considered. As with all patients with GERD, first-line appropriate initial therapy is rapid stabilization of severely treatment should focus on lifestyle and diet modifications. elevated BP and intravenous magnesium followed by imme Pharmacologic therapy includes antacids, H, blockers, and diate delivery of the fetus. Magnesium sulfate is the drug of proton pump inhibitor (PPI) therapy. In this patient with sig- choice for seizure prophylaxis for women with acute-onset nificant symptoms, an H, blocker such as famotidine should severe hypertension during pregnancy and the postpartum be added to lifestyle modifications as treatment for GERD. In period. Starting magnesium should not be delayed in the patients with advanced CKD, the dosing of H, blockers should setting of acute severe hypertension; it is recommended be decreased or the dosing interval increased as guided by regardless of whether the patient has gestational hyper- labeling instruction. tension with severe features, preeclampsia with severe In addition to their classic association with acute inter- features, or eclampsia. Acute kidney injury may persist for stitial nephritis/acute kidney injury, PPIs such as omepra- up to 48 hours following delivery; proteinuria may take zole (Option B) may contribute to the development and months to resolve. progression of CKD. The association has been observed in In large studies, intravenous dexamethasone therapy case-control studies and affirmed in a systematic review and (Option B) has not been shown to be efficacious in treatment meta-analysis. Although the evidence comes from obser- of severe preeclampsia or the HELLP syndrome. vational studies, caution is still advised when considering Intravenous eculizumab (Option C) is indicated for PPI use in patients with advanced CKD, particularly when patients with atypical hemolytic uremic syndrome with alternative therapies are available. deficiencies in the complement cascade. Atypical hemolytic Over-the-counter oral antacids containing calcium car- uremic syndrome does not cause liver dysfunction as seen bonate and magnesium hydroxide (Option C) are commonly in this patient. used to treat symptoms of GERD. However, patients with Distinguishing the HELLP syndrome from thrombotic advanced CKD are at risk for magnesium toxicity with the thrombocytopenic purpura (TTP) is important, as patients use of these antacids and therefore should be avoided. with TTP require fresh frozen plasma exchange (Option D) Sucralfate (Option D) is a sulfated polysaccharide com- and glucocorticoids. TTP is very uncommon in pregnancy, plexed with aluminum hydroxide used in the treatment of typically presents earlier in gestation, and is marked by an peptic ulcer disease. Sucralfate binds to injured mucosal sur- even more profound decrease in hemoglobin and platelet face, promotes healing, and provides a barrier to peptic injury. count than seen in this patient. Sucralfate is less effective than PPI therapy for peptic ulcer Transfusion of packed red blood cells and platelets disease. Sucralfate has no role in the treatment of GERD due (Option E) is generally not recommended for patients in the to its short duration of action and reduced effectiveness com- absence of overt bleeding unless hemoglobin levels decrease pared with other therapies, including PPIs and H, blockers. to <7 g/dL (70 g/L) or platelet count decreases to <20,000/nL Finally, sucralfate contains aluminum, which may accumulate (20 x 109/L). in patients with advanced CKD and is thus not recommended.

e Indications for kidney biopsy include glomerular e Severe preeclampsia is identified by persistent systolic hematuria, severely increased albuminuria, acute or blood pressure >160 mm Hg or diastolic blood pressure chronic kidney disease of unclear cause, and kidney >110 mm Hg and end-organ damage. transplant dysfunction or monitoring. e Initial therapy for severe preeclampsia is magnesium, antihypertensive medication, and immediate delivery Bibliography of the fetus. Luciano RL, Moeckel GW. Update on the native kidney biopsy: core curricu- lum 2019. Am J Kidney Dis. 2019;73:404-415. [PMID: 30661724] doi:10.1053/j.ajkd.2018.10.011 Bibliography ACOG committee opinion no. 767 summary: emergent therapy for acute- onset, severe hypertension during pregnancy and the postpartum period [editorial]. Obstet Gynecol. 2019;133:409-412. [PMID: 30681541] doi:10. 1097/AOG.0000000000003082 Ww Item 9 Answer: A ch 4 Educational Objective: Treat severe preeclampsia. = = The most appropriate treatment is to continue current Item 10 Answer: A oO therapy (Option A). Severe preeclampsia is identified by os Educational Objective: Treat gastroesophageal reflux <= persistent systolic blood pressure (BP) >160 mm Hg or dia- ) disease in a patient with advanced chronic kidney disease. w stolic BP >110 mm Hg and end-organ damage. The HELLP od o (hemolysis, elevated liver enzymes, low platelets) syndrome The most appropriate additional therapy is famotidine = w may represent a severe form of preeclampsia. In the HELLP (Option A). This patient has stage G4 chronic kidney disease = 4 syndrome, the hemolytic anemia, thrombocytopenia, and (CKD) and symptoms of his gastroesophageal reflux disease liver dysfunction are more prominent, whereas severe pre (GERD). In patients with CKD, the nephrotoxic risk of med- eclampsia has greater BP elevations. This patient has severe ication or treatment used for comorbid medical conditions preeclampsia with features of the HELLP syndrome. The must be considered. As with all patients with GERD, first-line appropriate initial therapy is rapid stabilization of severely treatment should focus on lifestyle and diet modifications. elevated BP and intravenous magnesium followed by imme Pharmacologic therapy includes antacids, H, blockers, and diate delivery of the fetus. Magnesium sulfate is the drug of proton pump inhibitor (PPI) therapy. In this patient with sig- choice for seizure prophylaxis for women with acute-onset nificant symptoms, an H, blocker such as famotidine should severe hypertension during pregnancy and the postpartum be added to lifestyle modifications as treatment for GERD. In period. Starting magnesium should not be delayed in the patients with advanced CKD, the dosing of H, blockers should setting of acute severe hypertension; it is recommended be decreased or the dosing interval increased as guided by regardless of whether the patient has gestational hyper- labeling instruction. tension with severe features, preeclampsia with severe In addition to their classic association with acute inter- features, or eclampsia. Acute kidney injury may persist for stitial nephritis/acute kidney injury, PPIs such as omepra- up to 48 hours following delivery; proteinuria may take zole (Option B) may contribute to the development and months to resolve. progression of CKD. The association has been observed in In large studies, intravenous dexamethasone therapy case-control studies and affirmed in a systematic review and (Option B) has not been shown to be efficacious in treatment meta-analysis. Although the evidence comes from obser- of severe preeclampsia or the HELLP syndrome. vational studies, caution is still advised when considering Intravenous eculizumab (Option C) is indicated for PPI use in patients with advanced CKD, particularly when patients with atypical hemolytic uremic syndrome with alternative therapies are available. deficiencies in the complement cascade. Atypical hemolytic Over-the-counter oral antacids containing calcium car- uremic syndrome does not cause liver dysfunction as seen bonate and magnesium hydroxide (Option C) are commonly in this patient. used to treat symptoms of GERD. However, patients with Distinguishing the HELLP syndrome from thrombotic advanced CKD are at risk for magnesium toxicity with the thrombocytopenic purpura (TTP) is important, as patients use of these antacids and therefore should be avoided. with TTP require fresh frozen plasma exchange (Option D) Sucralfate (Option D) is a sulfated polysaccharide com- and glucocorticoids. TTP is very uncommon in pregnancy, plexed with aluminum hydroxide used in the treatment of typically presents earlier in gestation, and is marked by an peptic ulcer disease. Sucralfate binds to injured mucosal sur- even more profound decrease in hemoglobin and platelet face, promotes healing, and provides a barrier to peptic injury. count than seen in this patient. Sucralfate is less effective than PPI therapy for peptic ulcer Transfusion of packed red blood cells and platelets disease. Sucralfate has no role in the treatment of GERD due (Option E) is generally not recommended for patients in the to its short duration of action and reduced effectiveness com- absence of overt bleeding unless hemoglobin levels decrease pared with other therapies, including PPIs and H, blockers. to <7 g/dL (70 g/L) or platelet count decreases to <20,000/nL Finally, sucralfate contains aluminum, which may accumulate (20 x 109/L). in patients with advanced CKD and is thus not recommended. 125

Answers and Critiques evidence of hydroureter. Treatment with lithotripsy is a bet- ter option in this patient. e Proton pump inhibitors may contribute to the devel- opment and progression of chronic kidney disease and should be avoided. e Stone passage decreases with increasing size; only e H, blocker therapy can be considered for patients 50% of stones >6 mm will pass, and stones >10 mm with advanced chronic kidney disease provided are extremely unlikely to pass spontaneously. appropriate dosing is used. ¢ Urologic intervention is required in all patients with evidence of infection, acute kidney injury, intractable Bibliography pain, stones that fail to pass, or large stones that are Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between unlikely to pass. proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. > 2018;33:331-342. [PMID: 28339835] doi:10.1093/ndt/gfw470 = Bibliography wn Preminger GM, Tiselius HG, Assimos DG, et al; EAU/AUA Nephrolithiasis = Guideline Panel. 2007 guideline for the management of ureteral calculi. @o = J Urol. 2007;178:2418-2434. [PMID: 17993340] wn & Item 11 Answer: B s 2. Educational Objective: Treat a kidney stone with a lithotripsy. Item 12 Answer: C th =. Educational Objective: Diagnose drug-induced 2 The most appropriate treatment is lithotripsy (Option B). A i=] hypomagnesemia as a cause of hypokalemia. @ kidney stone >10 mm, as seen in this patient, is unlikely to n pass into the bladder and must be removed promptly because This most likely cause of this patient’s hypokalemia is sec- there are signs of ureteral obstruction, which can result in ondary hypomagnesemia caused by pantoprazole (Option kidney damage. Acute management of symptomatic neph- C). The potassium channel in the distal nephron is gated by rolithiasis is aimed at pain management and facilitation of magnesium and, in states of hypomagnesemia, remains open stone passage. Pain can be relieved by NSAIDs and opioids as with subsequent renal losses of potassium. Hypomagnese- needed. Stone passage decreases with increasing size. Only mia has become increasingly recognized in patients taking 50% of stones >6 mm will pass, generally within 2 weeks, and proton pump inhibitors (PPIs) and is listed as a potential stones >10 mm are extremely unlikely to pass spontaneously. adverse effect in package inserts. The longer duration a per- Urologic intervention is required in all patients with evidence son has been taking PPIs, the greater the likelihood of devel- of infection, acute kidney injury, intractable pain, and stones oping hypomagnesemia. Because urine magnesium levels that fail to pass. The most effective method for removal of this are low in patients with hypomagnesemia, the presumed patient’s stone is to break it up using either shock wave or mechanism is believed to be inhibition of the magnesium laser lithotripsy. The former is noninvasive, whereas the latter transporters in the gastrointestinal tract. Recent genomic is accomplished using an ureteroscope and requires anes- analysis has identified a genetic polymorphism in the TRMP thesia. Both methods have similar rates of stone clearance. 6 magnesium transporter in patients with PPI-induced hypo- Laser lithotripsy is more expensive but is associated with less magnesemia. Until the hypomagnesemia is corrected, the postlithotripsy discomfort. kidney will continue to waste potassium, making correction Administering intravenous 0.9% saline (Option A) of hypokalemia difficult. would not be beneficial. There is no evidence that increasing Sodium-glucose transporter 2 (SGLT2) inhibitors such urinary flow with the use of intravenous hydration results as canagliflozin (Option A) have been associated with a in a more rapid transit of kidney stones or decreased use small increase in magnesium levels and would not be asso- of pain medication but may add to discomfort and patient ciated with this patient’s hypomagnesemia. Patients with inconvenience. type 2 diabetes mellitus frequently have mild hypomag- Although tamsulosin (Option C) has been used to facil- nesemia, which has been postulated to be secondary to itate stone passage, data suggest it may be less effective than insulin resistance. The cause of the increase in magnesium previously believed reported. The data, however, remain noted with SGLT2 inhibitors is unclear but may be related to controversial and, because risk is minimal, use of tamsu- improvement in insulin resistance or possibly a direct effect losin to aid in stone passage can still be considered. Trials on magnesium transporters in the kidney. of assisted passage may last up to 4 weeks. Regardless, this Lisinopril (Option B), an ACE inhibitor, has minimal if patient’s stone is too large to pass into the ureter with or any effect on magnesium levels. By decreasing aldosterone without tamsulosin therapy. levels, these medications are associated with hyperkalemia. Observation (Option D) with frequent reevaluation may Although diuretic use can cause both hypokalemia and be an acceptable strategy for select patients with small stones hypomagnesemia, this is usually associated with a meta- and mild, easily managed pain, no evidence of infection, bolic alkalosis. Because this patient’s serum bicarbonate is and no evidence of impending kidney damage. This patient not increased, surreptitious diuretic use (Option D) is a less has a stone that is too large to pass spontaneously and has likely cause of her hypokalemia.

evidence of hydroureter. Treatment with lithotripsy is a bet- ter option in this patient. e Proton pump inhibitors may contribute to the devel- opment and progression of chronic kidney disease and should be avoided. e Stone passage decreases with increasing size; only e H, blocker therapy can be considered for patients 50% of stones >6 mm will pass, and stones >10 mm with advanced chronic kidney disease provided are extremely unlikely to pass spontaneously. appropriate dosing is used. ¢ Urologic intervention is required in all patients with evidence of infection, acute kidney injury, intractable Bibliography pain, stones that fail to pass, or large stones that are Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between unlikely to pass. proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. > 2018;33:331-342. [PMID: 28339835] doi:10.1093/ndt/gfw470 = Bibliography wn Preminger GM, Tiselius HG, Assimos DG, et al; EAU/AUA Nephrolithiasis = Guideline Panel. 2007 guideline for the management of ureteral calculi. @o = J Urol. 2007;178:2418-2434. [PMID: 17993340] wn & Item 11 Answer: B s 2. Educational Objective: Treat a kidney stone with a lithotripsy. Item 12 Answer: C th =. Educational Objective: Diagnose drug-induced 2 The most appropriate treatment is lithotripsy (Option B). A i=] hypomagnesemia as a cause of hypokalemia. @ kidney stone >10 mm, as seen in this patient, is unlikely to n pass into the bladder and must be removed promptly because This most likely cause of this patient’s hypokalemia is sec- there are signs of ureteral obstruction, which can result in ondary hypomagnesemia caused by pantoprazole (Option kidney damage. Acute management of symptomatic neph- C). The potassium channel in the distal nephron is gated by rolithiasis is aimed at pain management and facilitation of magnesium and, in states of hypomagnesemia, remains open stone passage. Pain can be relieved by NSAIDs and opioids as with subsequent renal losses of potassium. Hypomagnese- needed. Stone passage decreases with increasing size. Only mia has become increasingly recognized in patients taking 50% of stones >6 mm will pass, generally within 2 weeks, and proton pump inhibitors (PPIs) and is listed as a potential stones >10 mm are extremely unlikely to pass spontaneously. adverse effect in package inserts. The longer duration a per- Urologic intervention is required in all patients with evidence son has been taking PPIs, the greater the likelihood of devel- of infection, acute kidney injury, intractable pain, and stones oping hypomagnesemia. Because urine magnesium levels that fail to pass. The most effective method for removal of this are low in patients with hypomagnesemia, the presumed patient’s stone is to break it up using either shock wave or mechanism is believed to be inhibition of the magnesium laser lithotripsy. The former is noninvasive, whereas the latter transporters in the gastrointestinal tract. Recent genomic is accomplished using an ureteroscope and requires anes- analysis has identified a genetic polymorphism in the TRMP thesia. Both methods have similar rates of stone clearance. 6 magnesium transporter in patients with PPI-induced hypo- Laser lithotripsy is more expensive but is associated with less magnesemia. Until the hypomagnesemia is corrected, the postlithotripsy discomfort. kidney will continue to waste potassium, making correction Administering intravenous 0.9% saline (Option A) of hypokalemia difficult. would not be beneficial. There is no evidence that increasing Sodium-glucose transporter 2 (SGLT2) inhibitors such urinary flow with the use of intravenous hydration results as canagliflozin (Option A) have been associated with a in a more rapid transit of kidney stones or decreased use small increase in magnesium levels and would not be asso- of pain medication but may add to discomfort and patient ciated with this patient’s hypomagnesemia. Patients with inconvenience. type 2 diabetes mellitus frequently have mild hypomag- Although tamsulosin (Option C) has been used to facil- nesemia, which has been postulated to be secondary to itate stone passage, data suggest it may be less effective than insulin resistance. The cause of the increase in magnesium previously believed reported. The data, however, remain noted with SGLT2 inhibitors is unclear but may be related to controversial and, because risk is minimal, use of tamsu- improvement in insulin resistance or possibly a direct effect losin to aid in stone passage can still be considered. Trials on magnesium transporters in the kidney. of assisted passage may last up to 4 weeks. Regardless, this Lisinopril (Option B), an ACE inhibitor, has minimal if patient’s stone is too large to pass into the ureter with or any effect on magnesium levels. By decreasing aldosterone without tamsulosin therapy. levels, these medications are associated with hyperkalemia. Observation (Option D) with frequent reevaluation may Although diuretic use can cause both hypokalemia and be an acceptable strategy for select patients with small stones hypomagnesemia, this is usually associated with a meta- and mild, easily managed pain, no evidence of infection, bolic alkalosis. Because this patient’s serum bicarbonate is and no evidence of impending kidney damage. This patient not increased, surreptitious diuretic use (Option D) is a less has a stone that is too large to pass spontaneously and has likely cause of her hypokalemia. 126

Answers and Critiques Labetalol (Option C) and other antihypertensive agents are not indicated, as treatment of chronic hypertension in e Proton pump inhibitors are a cause of hypomagnesemia, pregnancy is not needed if the patient's blood pressure is which typically occurs after long-term use. <160/110 mm Hg and there is no evidence of end-organ e Magnesium deficiency is an important cause of damage, as seen in this patient. hypokalemia.

Labetalol (Option C) and other antihypertensive agents are not indicated, as treatment of chronic hypertension in e Proton pump inhibitors are a cause of hypomagnesemia, pregnancy is not needed if the patient's blood pressure is which typically occurs after long-term use. <160/110 mm Hg and there is no evidence of end-organ e Magnesium deficiency is an important cause of damage, as seen in this patient. hypokalemia. Bibliography e For pregnant women with chronic hypertension, Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton guidelines recommend only treating persistent sys- pump inhibitors linked to hypomagnesemia: a systematic review and tolic 2160 mm Hg or diastolic 2110 mm Hg blood meta-analysis of observational studies. Ren Fail. 2015;37:1237-1241. [PMID: 26108134] doi:10.3109/0886022X.2015.1057800 pressure in the absence of end-organ damage to avoid overtreatment of hypertension and associated fetal risk. ~” @ = Item 13 Answer: D ¢ Treatment of chronic hypertension (<160/110 mm Hg) = during pregnancy is not associated with improved Educational Objective: Manage chronic hypertension in 7 a pregnant patient. fetal outcomes. cs) a=] = No further management other than clinical monitoring © Bibliography (Option D) is needed for this pregnant patient with chronic ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet a @ hypertension. Chronic hypertension is defined as hyperten- Gynecol. 2019;133:e26-e50. [PMID: 30575676] doi:10.1097/AOG. = 0000000000003020 wn sion starting before pregnancy or before 20 weeks of gestation. = According to the American College of Cardiology/American <=

Bibliography e For pregnant women with chronic hypertension, Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton guidelines recommend only treating persistent sys- pump inhibitors linked to hypomagnesemia: a systematic review and tolic 2160 mm Hg or diastolic 2110 mm Hg blood meta-analysis of observational studies. Ren Fail. 2015;37:1237-1241. [PMID: 26108134] doi:10.3109/0886022X.2015.1057800 pressure in the absence of end-organ damage to avoid overtreatment of hypertension and associated fetal risk. ~” @ = Item 13 Answer: D ¢ Treatment of chronic hypertension (<160/110 mm Hg) = during pregnancy is not associated with improved Educational Objective: Manage chronic hypertension in 7 a pregnant patient. fetal outcomes. cs) a=] = No further management other than clinical monitoring © Bibliography (Option D) is needed for this pregnant patient with chronic ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet a @ hypertension. Chronic hypertension is defined as hyperten- Gynecol. 2019;133:e26-e50. [PMID: 30575676] doi:10.1097/AOG. = 0000000000003020 wn sion starting before pregnancy or before 20 weeks of gestation. = According to the American College of Cardiology/American <= Heart Association guidelines, and adopted by the American Item 14 Answer: C College of Obstetricians and Gynecologists (ACOG), the diag- Educational Objective: Diagnose white coat hypertension nosis of hypertension before pregnancy is based on systolic using ambulatory blood pressure monitoring. blood pressure >130 mm Hg and diastolic blood pressure >80 mm Hg. This patient is at 24 weeks’ gestation and has The most appropriate management is to perform ambulatory no proteinuria or other evidence of end-organ damage; the blood pressure monitoring (ABPM) (Option C) to evaluate diagnosis is most consistent with chronic hypertension. A for white coat hypertension. White coat hypertension, also 2014 Cochrane systematic review of 49 trials (4723 women) termed isolated clinic or office hypertension, refers to ele- concluded that treatment of mild-to-moderate hypertension vated blood pressure (BP) measured in the office, but normal reduced the risk for developing severe hypertension but had out-of-office BP averages. According to guideline recommen- no effect on the incidence of preeclampsia, preterm birth, dations, in adults with untreated systolic BP >130 mm Hg but fetal death, fetal growth restriction, or any other measured <160 mm Hg or diastolic BP >80 mm Hg but <100 mm Hg, it is outcome. Antihypertensive treatment is not necessary at this reasonable to screen for white coat hypertension using either time. For pregnant women with chronic hypertension, the ABPM or home BP monitoring measurements obtained by 2019 ACOG Taskforce on Hypertension in Pregnancy rec- the patient. Before white coat hypertension is diagnosed, the ommends only treating persistent systolic blood pressure reliability of out-of-office measurements must be confirmed; 2160 mm Hg or diastolic >110 mm Hg to avoid overtreatment of for example, the patient’s home BP monitor should be cali- hypertension and associated fetal risk. In the setting of comor- brated against the office sphygmomanometer or, preferably, bidities or underlying impaired kidney function, treating at BP should be measured by an ABPM device. In patients with lower blood pressure thresholds may be appropriate. Blood white coat hypertension, annual follow-up with out-of-office pressure goals with medications are 120-159/80-109 mm Hg. BP measurements should be considered to determine if con- First-line agents are labetalol, nifedipine, and methyldopa. version to sustained hypertension has occurred. Early delivery of the fetus (Option A) would be recom- Initiating chlorthalidone (Option A), a thiazide diuretic, mended if the patient had preeclampsia, which is defined is a reasonable initial therapy in patients with documented by new-onset hypertension that occurs after 20 weeks’ hypertension. Chlorthalidone is not indicated in this patient gestation associated proteinuria or end-organ damage. The unless hypertension is confirmed using ABPM or home BP absence of proteinuria and end-organ involvement in this monitoring. patient is not consistent with preeclampsia. CT angiography, MR angiography, and duplex Doppler Although thiazide diuretics such as hydrochlorothi- ultrasonography are imaging modalities used to diagnose azide (Option B) can be used in pregnancy, this patient’s renovascular hypertension. Routine testing for renovascular blood pressure does not warrant treatment at this time. disease may not change management for patients with ath- Furthermore, diuretics are considered second-line anti- erosclerotic renovascular disease, because data suggest that hypertensive agents during pregnancy and should be used medical therapy may be as beneficial as invasive procedures. with caution in pregnant patients, as they may induce However, in young patients with resistant hypertension and oligohydramnios. a high clinical suspicion for fibromuscular dysplasia (e.g.,

Heart Association guidelines, and adopted by the American Item 14 Answer: C College of Obstetricians and Gynecologists (ACOG), the diag- Educational Objective: Diagnose white coat hypertension nosis of hypertension before pregnancy is based on systolic using ambulatory blood pressure monitoring. blood pressure >130 mm Hg and diastolic blood pressure >80 mm Hg. This patient is at 24 weeks’ gestation and has The most appropriate management is to perform ambulatory no proteinuria or other evidence of end-organ damage; the blood pressure monitoring (ABPM) (Option C) to evaluate diagnosis is most consistent with chronic hypertension. A for white coat hypertension. White coat hypertension, also 2014 Cochrane systematic review of 49 trials (4723 women) termed isolated clinic or office hypertension, refers to ele- concluded that treatment of mild-to-moderate hypertension vated blood pressure (BP) measured in the office, but normal reduced the risk for developing severe hypertension but had out-of-office BP averages. According to guideline recommen- no effect on the incidence of preeclampsia, preterm birth, dations, in adults with untreated systolic BP >130 mm Hg but fetal death, fetal growth restriction, or any other measured <160 mm Hg or diastolic BP >80 mm Hg but <100 mm Hg, it is outcome. Antihypertensive treatment is not necessary at this reasonable to screen for white coat hypertension using either time. For pregnant women with chronic hypertension, the ABPM or home BP monitoring measurements obtained by 2019 ACOG Taskforce on Hypertension in Pregnancy rec- the patient. Before white coat hypertension is diagnosed, the ommends only treating persistent systolic blood pressure reliability of out-of-office measurements must be confirmed; 2160 mm Hg or diastolic >110 mm Hg to avoid overtreatment of for example, the patient’s home BP monitor should be cali- hypertension and associated fetal risk. In the setting of comor- brated against the office sphygmomanometer or, preferably, bidities or underlying impaired kidney function, treating at BP should be measured by an ABPM device. In patients with lower blood pressure thresholds may be appropriate. Blood white coat hypertension, annual follow-up with out-of-office pressure goals with medications are 120-159/80-109 mm Hg. BP measurements should be considered to determine if con- First-line agents are labetalol, nifedipine, and methyldopa. version to sustained hypertension has occurred. Early delivery of the fetus (Option A) would be recom- Initiating chlorthalidone (Option A), a thiazide diuretic, mended if the patient had preeclampsia, which is defined is a reasonable initial therapy in patients with documented by new-onset hypertension that occurs after 20 weeks’ hypertension. Chlorthalidone is not indicated in this patient gestation associated proteinuria or end-organ damage. The unless hypertension is confirmed using ABPM or home BP absence of proteinuria and end-organ involvement in this monitoring. patient is not consistent with preeclampsia. CT angiography, MR angiography, and duplex Doppler Although thiazide diuretics such as hydrochlorothi- ultrasonography are imaging modalities used to diagnose azide (Option B) can be used in pregnancy, this patient’s renovascular hypertension. Routine testing for renovascular blood pressure does not warrant treatment at this time. disease may not change management for patients with ath- Furthermore, diuretics are considered second-line anti- erosclerotic renovascular disease, because data suggest that hypertensive agents during pregnancy and should be used medical therapy may be as beneficial as invasive procedures. with caution in pregnant patients, as they may induce However, in young patients with resistant hypertension and oligohydramnios. a high clinical suspicion for fibromuscular dysplasia (e.g., 127

Answers and Critiques sudden onset of resistant hypertension at a young age, pres- In patients with normal kidney function, intravenous ence of an abdominal bruit), renal artery imaging may be furosemide (Option B), a loop diuretic, will increase kidney considered. This patient has no indication for renal artery magnesium excretion; treatment would not be beneficial in imaging (Option B). this patient with late-stage chronic kidney disease. Rechecking this patient’s BP in the office in 3 months Intravenous sodium bicarbonate (Option C) is associ- (Option D) is not appropriate management, as elevated office ated with a decrease in ionized calcium. Although in vitro BP should be confirmed using out-of-office measurements. studies suggest a similar effect on ionized magnesium, human studies have not been done to support the use of sodium bicarbonate in the treatment of hypermagnesemia. ¢ White coat hypertension refers to elevated blood pres- Patiromer (Option D) is a cation exchanger that is used sure measured in the office, but normal out-of-office to manage chronic elevations of serum potassium. Although measurements. patiromer has been associated with hypomagnesemia, this > e In adults with untreated systolic blood pressure agent has a relative slow onset of action (1 to 4 hours) and s wn >130 mm Hg but <160 mm Hg or diastolic blood pres- would not be effective acutely and thus not an appropriate = treatment for this patient. @o sure >80 mm Hg but <100 mm Hg, it is reasonable to = wn screen for white coat hypertension using either re) i | ambulatory blood pressure monitoring or home blood Q. e¢ Hypermagnesemia decreases neural transmission, pressure monitoring. oO resulting in weakness, and blocks both calcium and oe =. potassium channels, resulting in hypotension and 2 Bibliography = bradycardia. Oo Roerecke M, Kaczorowski J, Myers MG. Comparing automated office blood wv pressure readings with other methods of blood pressure measurement e Symptomatic hypermagnesemia (serum magnesium for identifying patients with possible hypertension: a systematic review and meta-analysis. JAMA Intern Med. 2019;179:351-362. [PMID: level >4.8 mg/dL [2.0 mmol/L]) is immediately treated 30715088] doi:10.1001/jamainternmed.2018.6551 with intravenous calcium gluconate while awaiting hemodialysis.

sudden onset of resistant hypertension at a young age, pres- In patients with normal kidney function, intravenous ence of an abdominal bruit), renal artery imaging may be furosemide (Option B), a loop diuretic, will increase kidney considered. This patient has no indication for renal artery magnesium excretion; treatment would not be beneficial in imaging (Option B). this patient with late-stage chronic kidney disease. Rechecking this patient’s BP in the office in 3 months Intravenous sodium bicarbonate (Option C) is associ- (Option D) is not appropriate management, as elevated office ated with a decrease in ionized calcium. Although in vitro BP should be confirmed using out-of-office measurements. studies suggest a similar effect on ionized magnesium, human studies have not been done to support the use of sodium bicarbonate in the treatment of hypermagnesemia. ¢ White coat hypertension refers to elevated blood pres- Patiromer (Option D) is a cation exchanger that is used sure measured in the office, but normal out-of-office to manage chronic elevations of serum potassium. Although measurements. patiromer has been associated with hypomagnesemia, this > e In adults with untreated systolic blood pressure agent has a relative slow onset of action (1 to 4 hours) and s wn >130 mm Hg but <160 mm Hg or diastolic blood pres- would not be effective acutely and thus not an appropriate = treatment for this patient. @o sure >80 mm Hg but <100 mm Hg, it is reasonable to = wn screen for white coat hypertension using either re) i | ambulatory blood pressure monitoring or home blood Q. e¢ Hypermagnesemia decreases neural transmission, pressure monitoring. oO resulting in weakness, and blocks both calcium and oe =. potassium channels, resulting in hypotension and 2 Bibliography = bradycardia. Oo Roerecke M, Kaczorowski J, Myers MG. Comparing automated office blood wv pressure readings with other methods of blood pressure measurement e Symptomatic hypermagnesemia (serum magnesium for identifying patients with possible hypertension: a systematic review and meta-analysis. JAMA Intern Med. 2019;179:351-362. [PMID: level >4.8 mg/dL [2.0 mmol/L]) is immediately treated 30715088] doi:10.1001/jamainternmed.2018.6551 with intravenous calcium gluconate while awaiting hemodialysis. Item 15 Answer: A Bibliography Reddy ST, Soman SS, Yee J. Magnesium balance and measurement. Adv Educational Objective: Treat hypermagnesemia in a Chronic Kidney Dis. 2018;25:224-229. [PMID: 29793660] doi:10.1053/j. patient with chronic kidney disease. ackd.2018.03.002

Item 15 Answer: A Bibliography Reddy ST, Soman SS, Yee J. Magnesium balance and measurement. Adv Educational Objective: Treat hypermagnesemia in a Chronic Kidney Dis. 2018;25:224-229. [PMID: 29793660] doi:10.1053/j. patient with chronic kidney disease. ackd.2018.03.002 The most appropriate immediate treatment is intrave- nous calcium gluconate (Option A). Hypermagnesemia Item 16 Answer: A is defined by a serum magnesium level of >2.4 mg/dL Educational Objective: Treat acute kidney injury with (0.99 mmol/L). Hypermagnesemia occurs infrequently renal replacement therapy. and most commonly results from excessive intake in the setting of decreased kidney function. Laboratory analysis The most appropriate renal replacement therapy (RRT) is often shows hypocalcemia. In patients with significant continuous RRT (CRRT) (Option A). RRT is used to manage kidney disease, use of magnesium laxatives can cause sig- the urgent complications of severe acute kidney injury (AKI). nificant elevation of serum magnesium levels and should including hyperkalemia, metabolic acidosis, volume overload be avoided in these patients. Many medications such as refractory to diuretics, uremic manifestations, and dialyzable antacids and magnesium sulfate used in the treatment of toxins. In patients with AKI, RRT options include intermittent refractory asthma and preeclampsia are other sources of hemodialysis (IHD); CRRT; “hybrid” therapies such as pro magnesium. Hypermagnesemia decreases neural transmis- longed intermittent RRT (PIRRT); and peritoneal dialysis. This sion, resulting in weakness, as seen in this patient, which patient has AKI, metabolic acidosis, hyperkalemia, and vol can progress to paralysis. Hypermagnesemia also blocks ume overload. In patients who are hemodynamically unsta- calcium and potassium channels, resulting in hypotension ble, CRRT is preferred because it is administered 24 hours per and bradycardia. These effects become apparent when the day, removing solutes and fluid much more slowly than IHD serum magnesium level is >4.8 mg/dL (2.0 mmol/L). Pre- and resulting in better hemodynamic tolerance. However, vention is the key to management of hypermagnesemia by randomized clinical trials have not shown a survival benefit avoiding magnesium-containing medications in patients of CRRT over IHD or PIRRT for critically ill patients with AKI. with reduced kidney function. The immediate treatment Peritoneal dialysis (Option B) is not as effective as the for symptomatic hypermagnesemia is intravenous calcium other types of RRT but may be useful when other types are gluconate. Calcium rapidly antagonizes the cardiovascular unavailable or vascular access cannot be obtained. and neuromuscular effects of hypermagnesemia. This will This patient has life-threatening electrolyte abnormali allow time to set up and initiate hemodialysis, which is the ties and no immediate prospect of kidney function recovery. definitive treatment to lower magnesium levels in patients Therefore, continuation of current management (Option C) with severe hypermagnesemia. is unacceptable.

The most appropriate immediate treatment is intrave- nous calcium gluconate (Option A). Hypermagnesemia Item 16 Answer: A is defined by a serum magnesium level of >2.4 mg/dL Educational Objective: Treat acute kidney injury with (0.99 mmol/L). Hypermagnesemia occurs infrequently renal replacement therapy. and most commonly results from excessive intake in the setting of decreased kidney function. Laboratory analysis The most appropriate renal replacement therapy (RRT) is often shows hypocalcemia. In patients with significant continuous RRT (CRRT) (Option A). RRT is used to manage kidney disease, use of magnesium laxatives can cause sig- the urgent complications of severe acute kidney injury (AKI). nificant elevation of serum magnesium levels and should including hyperkalemia, metabolic acidosis, volume overload be avoided in these patients. Many medications such as refractory to diuretics, uremic manifestations, and dialyzable antacids and magnesium sulfate used in the treatment of toxins. In patients with AKI, RRT options include intermittent refractory asthma and preeclampsia are other sources of hemodialysis (IHD); CRRT; “hybrid” therapies such as pro magnesium. Hypermagnesemia decreases neural transmis- longed intermittent RRT (PIRRT); and peritoneal dialysis. This sion, resulting in weakness, as seen in this patient, which patient has AKI, metabolic acidosis, hyperkalemia, and vol can progress to paralysis. Hypermagnesemia also blocks ume overload. In patients who are hemodynamically unsta- calcium and potassium channels, resulting in hypotension ble, CRRT is preferred because it is administered 24 hours per and bradycardia. These effects become apparent when the day, removing solutes and fluid much more slowly than IHD serum magnesium level is >4.8 mg/dL (2.0 mmol/L). Pre- and resulting in better hemodynamic tolerance. However, vention is the key to management of hypermagnesemia by randomized clinical trials have not shown a survival benefit avoiding magnesium-containing medications in patients of CRRT over IHD or PIRRT for critically ill patients with AKI. with reduced kidney function. The immediate treatment Peritoneal dialysis (Option B) is not as effective as the for symptomatic hypermagnesemia is intravenous calcium other types of RRT but may be useful when other types are gluconate. Calcium rapidly antagonizes the cardiovascular unavailable or vascular access cannot be obtained. and neuromuscular effects of hypermagnesemia. This will This patient has life-threatening electrolyte abnormali allow time to set up and initiate hemodialysis, which is the ties and no immediate prospect of kidney function recovery. definitive treatment to lower magnesium levels in patients Therefore, continuation of current management (Option C) with severe hypermagnesemia. is unacceptable. 128

Answers and Critiques C) All of the loop diuretics produce the same diuresis when Surreptitious furosemide use (Option B) would be given at equipotent doses. The patient has been unrespon- expected to result in a metabolic alkalosis, not metabolic co NT. sive to escalating doses of furosemide; therefore, switching acidosis. to another loop diuretic such as intravenous bumetanide Renal causes of normal anion gap metabolic acidosis (Option D) is unlikely to result in a significant diuresis and are due to specific defects in bicarbonate reclamation (type will not address this patient's acidemia. 2 renal tubular acidosis [RTA]) or in hydrogen ion secretion (type 1 RTA). Topiramate (Option D) can cause both type 1 and type 2 RTA. The urine anion gap due to type 1 RTA is ¢ Continuous renal replacement therapy is a preferred positive, which is not the case in this patient. modality of renal replacement therapy in patients with acute kidney injury and hemodynamic instabil-

C) All of the loop diuretics produce the same diuresis when Surreptitious furosemide use (Option B) would be given at equipotent doses. The patient has been unrespon- expected to result in a metabolic alkalosis, not metabolic co NT. sive to escalating doses of furosemide; therefore, switching acidosis. to another loop diuretic such as intravenous bumetanide Renal causes of normal anion gap metabolic acidosis (Option D) is unlikely to result in a significant diuresis and are due to specific defects in bicarbonate reclamation (type will not address this patient's acidemia. 2 renal tubular acidosis [RTA]) or in hydrogen ion secretion (type 1 RTA). Topiramate (Option D) can cause both type 1 and type 2 RTA. The urine anion gap due to type 1 RTA is ¢ Continuous renal replacement therapy is a preferred positive, which is not the case in this patient. modality of renal replacement therapy in patients with acute kidney injury and hemodynamic instabil- ity. e Normal anion gap metabolic acidosis can be caused by gastrointestinal bicarbonate loss, renal loss of wn e Randomized clinical trials have not showna survival o bicarbonate, or the inability of the kidney to excrete o benefit of continuous renal replacement therapy over acid. = intermittent hemodialysis or prolonged intermittent = renal replacement therapy for critically ill patients e A negative urine anion gap suggests appropriate wy kidney excretion of acid and therefore gastrointestinal sc with acute kidney injury. = bicarbonate loss as the cause of normal anion gap C}

ity. e Normal anion gap metabolic acidosis can be caused by gastrointestinal bicarbonate loss, renal loss of wn e Randomized clinical trials have not showna survival o bicarbonate, or the inability of the kidney to excrete o benefit of continuous renal replacement therapy over acid. = intermittent hemodialysis or prolonged intermittent = renal replacement therapy for critically ill patients e A negative urine anion gap suggests appropriate wy kidney excretion of acid and therefore gastrointestinal sc with acute kidney injury. = bicarbonate loss as the cause of normal anion gap C} Bibliography metabolic acidosis. 2 7) Gaudry S, Hajage D, Dreyfuss D. Initiation of renal-replacement therapy in = the intensive care unit. N Engl J Med. 2016;375:1901-1902. [PMID: wn

Bibliography metabolic acidosis. 2 7) Gaudry S, Hajage D, Dreyfuss D. Initiation of renal-replacement therapy in = the intensive care unit. N Engl J Med. 2016;375:1901-1902. [PMID: wn 27959653] Bibliography = J Rastegar M, Nagami GT. Non-anion gap metabolic acidosis: a clinical approach to evaluation. Am J Kidney Dis. 2017;69:296-301. [PMID: 28029394] Item 17 Answer: C doi:10.1053 /j.ajkd.2016.09.01

27959653] Bibliography = J Rastegar M, Nagami GT. Non-anion gap metabolic acidosis: a clinical approach to evaluation. Am J Kidney Dis. 2017;69:296-301. [PMID: 28029394] Item 17 Answer: C doi:10.1053 /j.ajkd.2016.09.01 Educational Objective: Identify laxative abuse as a cause of normal anion gap metabolic acidosis. item 18 Answer: D Laxative abuse (Option C) is the most likely cause of this Educational Objective: Manage stable renovascular patient’s normal anion gap metabolic acidosis. Normal anion hypertension. gap metabolic acidosis can be caused by gastrointestinal No additional diagnostic testing (Option D) is needed for this bicarbonate loss, renal loss of bicarbonate, or the inability of patient with stable renovascular hypertension. Clinical sus- the kidney to excrete acid. The normal physiologic response picion for renovascular hypertension is raised when patients to systemic acidosis is an increase in urine acid excretion. >55 years of age present with onset of severe hypertension and Therefore, an initial diagnostic step in normal anion gap meta- develop acute kidney injury (AKI) after initiation of an ACE bolic acidosis is to determine whether the kidney is appropri- inhibitor or angiotensin receptor blocker (ARB), or after con- ately excreting acid. Increased acid excretion by the kidney is trol of blood pressure (BP) to target goal. In addition, asym- reflected as a marked increase in urine ammonium. However, metry >1.5 cm in kidney sizes on imaging or the presence of a urine ammonium measurement is difficult to obtain. Because kidney <9 cm can also increase the probability. Patients such ammonium carries a positive charge, chloride is excreted as as this one with evidence of atherosclerotic cardiovascular the corresponding anion. Therefore, the amount of excreted disease should receive medical therapy, including lifestyle chloride increases as urine ammonium levels increase. The interventions, low-dose aspirin, BP control, guideline- urine anion gap can be used as an indicator of the ability of directed diabetes management, and high-intensity statin the kidney to excrete acid. The urine anion gap is calculated therapy. In patients with hypertension and chronic kidney as follows: disease (CKD) stage G3 or higher or stage G1 or G2 with albu- Urine Anion Gap = (Urine Sodium + Urine Potassium) minuria, treatment with an ACE inhibitor or ARB is recom- ~ Urine Chloride mended to slow kidney disease progression. In the context of increased urinary ammonium excre- Three randomized trials (STAR, ASTRAL, and CORAL) tion, therefore, the urine anion gap will be negative. The failed to show that renal artery angioplasty (Option A) con- negative urine anion gap in this patient (-6.0 mEq/L [-6.0 fers additional benefit above optimal medical therapy in mmol/L]) suggests appropriate renal excretion of acid and patients with renovascular hypertension and stable kid- therefore a gastrointestinal cause of the normal anion gap ney function. Patients who may benefit from percutaneous metabolic acidosis. In this patient, laxative abuse is a pos- angioplasty or surgical intervention include those with a sible, even likely, explanation. In addition, the low urine short duration of hypertension; atherosclerotic renovascu- potassium indicates appropriate renal compensation in con- lar disease refractory to optimal medical therapy; severe text of laxative-induced hypokalemia. hypertension or recurrent acute flash pulmonary edema; Salicylate toxicity (Option A) would be associated with AKI following treatment with an ACE inhibitor or ARB; pro- an anion gap, which is not present in this patient. gressive impaired kidney function believed to be caused by

Educational Objective: Identify laxative abuse as a cause of normal anion gap metabolic acidosis. item 18 Answer: D Laxative abuse (Option C) is the most likely cause of this Educational Objective: Manage stable renovascular patient’s normal anion gap metabolic acidosis. Normal anion hypertension. gap metabolic acidosis can be caused by gastrointestinal No additional diagnostic testing (Option D) is needed for this bicarbonate loss, renal loss of bicarbonate, or the inability of patient with stable renovascular hypertension. Clinical sus- the kidney to excrete acid. The normal physiologic response picion for renovascular hypertension is raised when patients to systemic acidosis is an increase in urine acid excretion. >55 years of age present with onset of severe hypertension and Therefore, an initial diagnostic step in normal anion gap meta- develop acute kidney injury (AKI) after initiation of an ACE bolic acidosis is to determine whether the kidney is appropri- inhibitor or angiotensin receptor blocker (ARB), or after con- ately excreting acid. Increased acid excretion by the kidney is trol of blood pressure (BP) to target goal. In addition, asym- reflected as a marked increase in urine ammonium. However, metry >1.5 cm in kidney sizes on imaging or the presence of a urine ammonium measurement is difficult to obtain. Because kidney <9 cm can also increase the probability. Patients such ammonium carries a positive charge, chloride is excreted as as this one with evidence of atherosclerotic cardiovascular the corresponding anion. Therefore, the amount of excreted disease should receive medical therapy, including lifestyle chloride increases as urine ammonium levels increase. The interventions, low-dose aspirin, BP control, guideline- urine anion gap can be used as an indicator of the ability of directed diabetes management, and high-intensity statin the kidney to excrete acid. The urine anion gap is calculated therapy. In patients with hypertension and chronic kidney as follows: disease (CKD) stage G3 or higher or stage G1 or G2 with albu- Urine Anion Gap = (Urine Sodium + Urine Potassium) minuria, treatment with an ACE inhibitor or ARB is recom- ~ Urine Chloride mended to slow kidney disease progression. In the context of increased urinary ammonium excre- Three randomized trials (STAR, ASTRAL, and CORAL) tion, therefore, the urine anion gap will be negative. The failed to show that renal artery angioplasty (Option A) con- negative urine anion gap in this patient (-6.0 mEq/L [-6.0 fers additional benefit above optimal medical therapy in mmol/L]) suggests appropriate renal excretion of acid and patients with renovascular hypertension and stable kid- therefore a gastrointestinal cause of the normal anion gap ney function. Patients who may benefit from percutaneous metabolic acidosis. In this patient, laxative abuse is a pos- angioplasty or surgical intervention include those with a sible, even likely, explanation. In addition, the low urine short duration of hypertension; atherosclerotic renovascu- potassium indicates appropriate renal compensation in con- lar disease refractory to optimal medical therapy; severe text of laxative-induced hypokalemia. hypertension or recurrent acute flash pulmonary edema; Salicylate toxicity (Option A) would be associated with AKI following treatment with an ACE inhibitor or ARB; pro- an anion gap, which is not present in this patient. gressive impaired kidney function believed to be caused by 129

Anawens and Gritkques bilateral renovascular disease; or unilateral stenosis affecting Kidney recovery from drug-induced AIN is usually a solitary functioning kidney. This patient has none of these complete if the drug is discontinued immediately after the indications. Finally, patients with advanced CKD or with onset of kidney injury; however, recovery may take weeks proteinuria >1000 mg/g, such as this patient, are less likely to several months. Kidney biopsy should be considered if to benefit from revascularization. there is no improvement in kidney function after 5 to 7 days Although CT angiography and MR angiography (Options of drug discontinuation. Early glucocorticoid administra- B, C) have higher diagnostic utility than ultrasonography, tion may limit damage associated with drug-induced AIN. these imaging studies may be potentially harmful in patients When there are no obvious signs and symptoms of infection with severe CKD, given the risk for contrast nephropathy and or toxic exposures, the most appropriate management is gadolinium-induced nephrogenic systemic fibrosis (with to discontinue high-probability medications and consider group 1 but not group 2 gadolinium-based contras media). initiating a course of oral glucocorticoids. In patients taking Renal duplex Doppler ultrasonography is a reasonable imag- multiple medications, it is reasonable to selectively discon- = ing modality in these patients if performed by experienced tinue the medications most likely causative of AIN. In this —] ” sonographers. Additional testing for renal vascular disease patient, the most appropriate course is to discontinue the = is not required in this patient and is not cost-effective, given naproxen and omeprazole. oO =“ 7.) that no interventions other than continuing the current Calcium channel blockers (amlodipine), statins (ator- w@ = medical management will be undertaken. vastatin), and angiotensin receptor blockers (losartan) are Qu. rarely associated with AIN (Options A-D). (2) = =. e In most patients with renal artery stenosis, the primary 2 = therapeutic intervention is medical management, e Medications, especially antibiotics, are the most com- i) an including correction of modifiable cardiovascular risk mon cause of acute interstitial nephritis. factors. e Acute interstitial nephritis can be caused by NSAIDs and proton pump inhibitors in the absence of fever, Bibliography rash, or eosinophilia. Cooper CJ, Murphy TP, Cutlip DE, et al; CORAL Investigators. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13-22. [PMID: 24245566] doi:10.1056/NEJMoa1310753 Bibliography Perazella MA. Clinical approach to diagnosing acute and chronic tubuloint- erstitial disease. Adv Chronic Kidney Dis. 2017;24:57-63. [PMID: 28284380] doi:10.1053/j.ackd.2016.08.003 Item 19 Answer: E Educational Objective: Manage acute interstitial nephritis in a patient taking multiple medications. Item 20 Answer: E

bilateral renovascular disease; or unilateral stenosis affecting Kidney recovery from drug-induced AIN is usually a solitary functioning kidney. This patient has none of these complete if the drug is discontinued immediately after the indications. Finally, patients with advanced CKD or with onset of kidney injury; however, recovery may take weeks proteinuria >1000 mg/g, such as this patient, are less likely to several months. Kidney biopsy should be considered if to benefit from revascularization. there is no improvement in kidney function after 5 to 7 days Although CT angiography and MR angiography (Options of drug discontinuation. Early glucocorticoid administra- B, C) have higher diagnostic utility than ultrasonography, tion may limit damage associated with drug-induced AIN. these imaging studies may be potentially harmful in patients When there are no obvious signs and symptoms of infection with severe CKD, given the risk for contrast nephropathy and or toxic exposures, the most appropriate management is gadolinium-induced nephrogenic systemic fibrosis (with to discontinue high-probability medications and consider group 1 but not group 2 gadolinium-based contras media). initiating a course of oral glucocorticoids. In patients taking Renal duplex Doppler ultrasonography is a reasonable imag- multiple medications, it is reasonable to selectively discon- = ing modality in these patients if performed by experienced tinue the medications most likely causative of AIN. In this —] ” sonographers. Additional testing for renal vascular disease patient, the most appropriate course is to discontinue the = is not required in this patient and is not cost-effective, given naproxen and omeprazole. oO =“ 7.) that no interventions other than continuing the current Calcium channel blockers (amlodipine), statins (ator- w@ = medical management will be undertaken. vastatin), and angiotensin receptor blockers (losartan) are Qu. rarely associated with AIN (Options A-D). (2) = =. e In most patients with renal artery stenosis, the primary 2 = therapeutic intervention is medical management, e Medications, especially antibiotics, are the most com- i) an including correction of modifiable cardiovascular risk mon cause of acute interstitial nephritis. factors. e Acute interstitial nephritis can be caused by NSAIDs and proton pump inhibitors in the absence of fever, Bibliography rash, or eosinophilia. Cooper CJ, Murphy TP, Cutlip DE, et al; CORAL Investigators. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13-22. [PMID: 24245566] doi:10.1056/NEJMoa1310753 Bibliography Perazella MA. Clinical approach to diagnosing acute and chronic tubuloint- erstitial disease. Adv Chronic Kidney Dis. 2017;24:57-63. [PMID: 28284380] doi:10.1053/j.ackd.2016.08.003 Item 19 Answer: E Educational Objective: Manage acute interstitial nephritis in a patient taking multiple medications. Item 20 Answer: E Educational Objective: Diagnose proximal renal tubule Naproxen and omeprazole should be discontinued (Option dysfunction as a cause of hypophosphatemia. E). Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI) and is characterized by inflam- The most likely cause of this patient’s hypophosphatemia is mation and edema of the interstitium. The classic clini- proximal renal tubular dysfunction (Option E). This patient cal presentation of fever, rash, and peripheral eosinophilia has ifosfamide-induced Fanconi syndrome. Ifosfamide metab- occurs in only 10% to 30% of patients with AIN. Urinary olites are toxic to the proximal tubule, resulting in a general- findings can include eosinophiluria, leukocytes, erythro- ized decrease in cell energetics and a decrease in transport of cytes, and leukocyte casts. Urine eosinophils are neither various substances across the luminal membrane, including sensitive nor specific for AIN. Drug-induced AIN, especially phosphorus, glucose, amino acids, and protons. In addition due to antibiotics, is the most common cause of AIN. Other to phosphate wasting, as identified by the fractional excretion causes include infection, systemic disease, and autoimmune of phosphorus >5%, this patient also has glycosuria despite disorders. Typically, the serum creatinine level gradually having a normal serum glucose; this is commonly seen in increases 7 to 10 days after drug exposure. Drug-induced AIN patients with ifosfamide-induced Fanconi syndrome. The uri- from NSAIDs, including selective cyclooxygenase-2 inhib- nalysis finding of proteinuria is most likely secondary to the itors, is usually not associated with fever, rash, or eosino- loss of amino acids in the urine. Mesna is a thiol compound philia and develops 6 to 18 months after drug exposure. AIN that, when delivered intravenously, inactivates acrolein in the from NSAIDs can be associated with the nephrotic syndrome urine to reduce the risk for bladder toxicity from cyclophos- due to minimal change glomerulopathy or membranous phamide and ifosfamide. Although mesna can prevent the nephropathy. Proton pump inhibitors are also associated hemorrhagic cystitis, it has not been demonstrated to prevent with AIN without fever, rash, and eosinophilia. The onset the tubular toxicity. The treatment of the hypophosphatemia of AIN with proton pump inhibitors is variable but typically in this disorder requires large quantities of phosphorus, typ- occurs 10 to 11 weeks after exposure. Proton pump inhibi- ically intravenously. tors are believed to be a risk factor for the development of Chronic kidney disease (Option A) is associated with chronic kidney disease. an increase in the serum phosphorus caused by a decrease

Educational Objective: Diagnose proximal renal tubule Naproxen and omeprazole should be discontinued (Option dysfunction as a cause of hypophosphatemia. E). Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI) and is characterized by inflam- The most likely cause of this patient’s hypophosphatemia is mation and edema of the interstitium. The classic clini- proximal renal tubular dysfunction (Option E). This patient cal presentation of fever, rash, and peripheral eosinophilia has ifosfamide-induced Fanconi syndrome. Ifosfamide metab- occurs in only 10% to 30% of patients with AIN. Urinary olites are toxic to the proximal tubule, resulting in a general- findings can include eosinophiluria, leukocytes, erythro- ized decrease in cell energetics and a decrease in transport of cytes, and leukocyte casts. Urine eosinophils are neither various substances across the luminal membrane, including sensitive nor specific for AIN. Drug-induced AIN, especially phosphorus, glucose, amino acids, and protons. In addition due to antibiotics, is the most common cause of AIN. Other to phosphate wasting, as identified by the fractional excretion causes include infection, systemic disease, and autoimmune of phosphorus >5%, this patient also has glycosuria despite disorders. Typically, the serum creatinine level gradually having a normal serum glucose; this is commonly seen in increases 7 to 10 days after drug exposure. Drug-induced AIN patients with ifosfamide-induced Fanconi syndrome. The uri- from NSAIDs, including selective cyclooxygenase-2 inhib- nalysis finding of proteinuria is most likely secondary to the itors, is usually not associated with fever, rash, or eosino- loss of amino acids in the urine. Mesna is a thiol compound philia and develops 6 to 18 months after drug exposure. AIN that, when delivered intravenously, inactivates acrolein in the from NSAIDs can be associated with the nephrotic syndrome urine to reduce the risk for bladder toxicity from cyclophos- due to minimal change glomerulopathy or membranous phamide and ifosfamide. Although mesna can prevent the nephropathy. Proton pump inhibitors are also associated hemorrhagic cystitis, it has not been demonstrated to prevent with AIN without fever, rash, and eosinophilia. The onset the tubular toxicity. The treatment of the hypophosphatemia of AIN with proton pump inhibitors is variable but typically in this disorder requires large quantities of phosphorus, typ- occurs 10 to 11 weeks after exposure. Proton pump inhibi- ically intravenously. tors are believed to be a risk factor for the development of Chronic kidney disease (Option A) is associated with chronic kidney disease. an increase in the serum phosphorus caused by a decrease 130

Saneere ane Caees in filtered phosphorus; this patient has a decrease in serum features suggesting an underlying rheumatologic or autoim- phosphorus, which is inconsistent with chronic kidney dis- mune disease signifies glomerular bleeding and precludes ease as a cause for hypophosphatemia. the need for cystoscopy. Three hormones are largely responsible for regulat- Ultrasonography (Option C) is the most commonly ing calcium and phosphorus homeostasis: parathyroid hor- used kidney imaging modality. It is easily available, safe, mone, vitamin D, and fibroblast growth factor 23 (FGF-23) and relatively inexpensive. Ultrasonography can demon- (Option B). FGF-23 is a peptide secreted by various types strate hydronephrosis, kidney size and cortical thickness, of bone cells. It acts on the kidney to induce phosphatu- echogenicity, and presence of cysts and tumors. Absence of ria and downregulates 1o-hydroxylase to inhibit synthesis hydronephrosis quickly rules out obstruction in most cases. of 1,25-dihydroxyvitamin D. Although sarcomas have been Echogenicity is the ability of a tissue to “bounce back” or associated with increased secretion of FGF-23 and severe return the ultrasound signal and is recognized as brighter phosphate wasting due to tumor-induced osteomalacia, this shades on the sonogram image. Echogenicity is nonspecific is extremely rare and would not explain the patient’s glycos- but implies acute or chronic parenchymal disease. Ultraso- wn o uria and proteinuria. nography is very useful in the evaluation of patients with 3

in filtered phosphorus; this patient has a decrease in serum features suggesting an underlying rheumatologic or autoim- phosphorus, which is inconsistent with chronic kidney dis- mune disease signifies glomerular bleeding and precludes ease as a cause for hypophosphatemia. the need for cystoscopy. Three hormones are largely responsible for regulat- Ultrasonography (Option C) is the most commonly ing calcium and phosphorus homeostasis: parathyroid hor- used kidney imaging modality. It is easily available, safe, mone, vitamin D, and fibroblast growth factor 23 (FGF-23) and relatively inexpensive. Ultrasonography can demon- (Option B). FGF-23 is a peptide secreted by various types strate hydronephrosis, kidney size and cortical thickness, of bone cells. It acts on the kidney to induce phosphatu- echogenicity, and presence of cysts and tumors. Absence of ria and downregulates 1o-hydroxylase to inhibit synthesis hydronephrosis quickly rules out obstruction in most cases. of 1,25-dihydroxyvitamin D. Although sarcomas have been Echogenicity is the ability of a tissue to “bounce back” or associated with increased secretion of FGF-23 and severe return the ultrasound signal and is recognized as brighter phosphate wasting due to tumor-induced osteomalacia, this shades on the sonogram image. Echogenicity is nonspecific is extremely rare and would not explain the patient’s glycos- but implies acute or chronic parenchymal disease. Ultraso- wn o uria and proteinuria. nography is very useful in the evaluation of patients with 3 Intracellular shifts of phosphorus (Option C) can occur undifferentiated acute kidney injury but is of limited useful- eS with administration of insulin, refeeding in individuals with ness in the evaluation of glomerulonephritis. 7 oO starvation, or secondary to respiratory alkalosis; none of Leukocyte esterase is an enzyme present in leukocytes. cs = these factors is present in this patient. A positive test suggests pyuria (=5 leukocytes/hpf). A positive © Patients with diabetes mellitus and hyperglycemia may nitrite test signifies the presence of gram-negative bacteria ” - o have hypophosphatemia caused by osmotic diuresis (Option capable of converting urine nitrates into nitrites. Dipstick = D). However, this patient has no evidence of hyperglycemia analysis for urinary tract infection is most helpful when both wn & or evidence of an ongoing osmotic diuresis such as hypoten- the leukocyte esterase and nitrite tests are concordant. This 4

Intracellular shifts of phosphorus (Option C) can occur undifferentiated acute kidney injury but is of limited useful- eS with administration of insulin, refeeding in individuals with ness in the evaluation of glomerulonephritis. 7 oO starvation, or secondary to respiratory alkalosis; none of Leukocyte esterase is an enzyme present in leukocytes. cs = these factors is present in this patient. A positive test suggests pyuria (=5 leukocytes/hpf). A positive © Patients with diabetes mellitus and hyperglycemia may nitrite test signifies the presence of gram-negative bacteria ” - o have hypophosphatemia caused by osmotic diuresis (Option capable of converting urine nitrates into nitrites. Dipstick = D). However, this patient has no evidence of hyperglycemia analysis for urinary tract infection is most helpful when both wn & or evidence of an ongoing osmotic diuresis such as hypoten- the leukocyte esterase and nitrite tests are concordant. This 4 sion or hypernatremia. patient’s microscopic urinalysis reveals pyuria and accounts for the positive leukocyte esterase test. In this case, pyuria would be an expected finding in a patient with the nephritic e In patients with hypophosphatemia, proximal renal syndrome. A urine culture (Option D) therefore is not needed. tubular phosphate dysfunction can be identified by a fractional excretion of phosphorus >5%. e Glomerular hematuria typically features dysmorphic

sion or hypernatremia. patient’s microscopic urinalysis reveals pyuria and accounts for the positive leukocyte esterase test. In this case, pyuria would be an expected finding in a patient with the nephritic e In patients with hypophosphatemia, proximal renal syndrome. A urine culture (Option D) therefore is not needed. tubular phosphate dysfunction can be identified by a fractional excretion of phosphorus >5%. e Glomerular hematuria typically features dysmorphic Bibliography erythrocytes (or acanthocytes) and/or erythrocyte Panezai MA, Owen C, Szerlip HM. Partial Fanconi syndrome induced by casts on urine sediment examination and is associated ifosfamide. Proc (Bayl Univ Med Cent). 2019;32:73-74. [PMID: 30956588] with proteinuria. doi:10.1080/08998280.2018.1536020

Bibliography erythrocytes (or acanthocytes) and/or erythrocyte Panezai MA, Owen C, Szerlip HM. Partial Fanconi syndrome induced by casts on urine sediment examination and is associated ifosfamide. Proc (Bayl Univ Med Cent). 2019;32:73-74. [PMID: 30956588] with proteinuria. doi:10.1080/08998280.2018.1536020 ¢ Undiagnosed glomerular hematuria is an indication for a kidney biopsy. Item 21 Answer: B Educational Objective: Diagnose glomerulonephritis. Bibliography Willis GC, Tewelde SZ. The approach to the patient with hematuria. Emerg The most appropriate test is kidney biopsy (Option B). This Med Clin North Am. 2019;37:755-769. [PMID: 31563206] doi:10.1016/j. emc.2019.07.011 patient likely has glomerulonephritis. Glomerular hematuria typically features tea- or brown-colored urine with dysmor- phic erythrocytes (or acanthocytes) and/or erythrocyte casts Item 22 Answer: A on urine sediment examination. Leukocyturia and leukocyte Educational Objective: Treat hypertension in a Black casts can be seen in patients, such as this one, with glomer- patient who is unresponsive to initial therapy. ulonephritis. Dysmorphic urinary erythrocytes are defined by their irregular (nonspherical) shape; acanthocytes are one The most appropriate additional treatment is amlodipine type of dysmorphic erythrocyte. Erythrocyte casts are recog- (Option A). In this patient, a blood pressure (BP) target nized by their cylindrical or tubular structure and inclusion <130/80 mm Hg is reasonable. As initial therapy, thiazide of small, agranular spherocytes and, when present, are spe- diuretics or calcium channel blockers (CCBs) are preferred cific for hematuria of glomerular origin. Indications for kid- in Black patients without chronic kidney disease or heart ney biopsy include glomerular hematuria, severely increased failure. These drugs are more effective in lowering BP than albuminuria, acute or chronic kidney disease of unclear cause are renin-angiotensin system (RAS) inhibitors (ACE inhibi- (in the absence of atrophic kidneys), and kidney transplant tors or angiotensin receptor blockers [ARBs]) or B-blockers dysfunction or monitoring. This patient with undiagnosed and more effective in reducing cardiovascular events than glomerular hematuria should have a kidney biopsy. are RAS inhibitors or o-blockers. Two or more antihyper- Cystoscopy (Option A) is indicated in the evaluation of tensive medications are recommended to achieve a BP target gross or microscopic hematuria of nonglomerular origin. of <130/80 mm Hg in most adults, especially Black adults, The presence of erythrocyte casts, proteinuria, and clinical with hypertension. According to the American College of

¢ Undiagnosed glomerular hematuria is an indication for a kidney biopsy. Item 21 Answer: B Educational Objective: Diagnose glomerulonephritis. Bibliography Willis GC, Tewelde SZ. The approach to the patient with hematuria. Emerg The most appropriate test is kidney biopsy (Option B). This Med Clin North Am. 2019;37:755-769. [PMID: 31563206] doi:10.1016/j. emc.2019.07.011 patient likely has glomerulonephritis. Glomerular hematuria typically features tea- or brown-colored urine with dysmor- phic erythrocytes (or acanthocytes) and/or erythrocyte casts Item 22 Answer: A on urine sediment examination. Leukocyturia and leukocyte Educational Objective: Treat hypertension in a Black casts can be seen in patients, such as this one, with glomer- patient who is unresponsive to initial therapy. ulonephritis. Dysmorphic urinary erythrocytes are defined by their irregular (nonspherical) shape; acanthocytes are one The most appropriate additional treatment is amlodipine type of dysmorphic erythrocyte. Erythrocyte casts are recog- (Option A). In this patient, a blood pressure (BP) target nized by their cylindrical or tubular structure and inclusion <130/80 mm Hg is reasonable. As initial therapy, thiazide of small, agranular spherocytes and, when present, are spe- diuretics or calcium channel blockers (CCBs) are preferred cific for hematuria of glomerular origin. Indications for kid- in Black patients without chronic kidney disease or heart ney biopsy include glomerular hematuria, severely increased failure. These drugs are more effective in lowering BP than albuminuria, acute or chronic kidney disease of unclear cause are renin-angiotensin system (RAS) inhibitors (ACE inhibi- (in the absence of atrophic kidneys), and kidney transplant tors or angiotensin receptor blockers [ARBs]) or B-blockers dysfunction or monitoring. This patient with undiagnosed and more effective in reducing cardiovascular events than glomerular hematuria should have a kidney biopsy. are RAS inhibitors or o-blockers. Two or more antihyper- Cystoscopy (Option A) is indicated in the evaluation of tensive medications are recommended to achieve a BP target gross or microscopic hematuria of nonglomerular origin. of <130/80 mm Hg in most adults, especially Black adults, The presence of erythrocyte casts, proteinuria, and clinical with hypertension. According to the American College of 131

(eee Cardiology/American Heart Association guideline, four drug gut, contributing to hypocalcemia. Hypocalcemia is a potent classes (thiazide diuretics, CCBs, ACE inhibitors, or ARBs) stimulus for further increases in PTH levels. Increased PTH lower BP and reduce cardiovascular or renal outcomes. Except levels result in reduced calcium excretion, increased calcium for the combination of ACE inhibitors and ARBs, regimens absorption from the gut, increased phosphorus excretion by containing a combination of these classes are reasonable to the kidneys, and activation of osteoclast bone resorption. As achieve the BP target. Furthermore, the combination of an CKD progresses, the kidney is unable to compensate for the ACE inhibitor or ARB with a CCB or thiazide diuretic produces increased release of phosphorus from bone, and phosphorus similar BP lowering in Black patients as in those of other racial levels rise. Disordered calcium and phosphate metabolism or ethnic groups. lead to several adverse pathologic effects, including vascular Doxazosin, hydralazine, and metoprolol (Options B-D) are calcification, increased risk for cardiovascular events, and not recommended drugs for either initial therapy or as add-on the altered-bone physiology of renal osteodystrophy. The 2017 therapy in patients with hypertension, regardless of race or Kidney Disease: Improving Global Outcomes (KDIGO) guide- cod ethnicity, without the presence of compelling indications. Dox- lines recommend that, in patients with CKD stages G3a to —J “ azosin might be considered in male patients with bothersome GS, elevated phosphorus levels should be lowered toward the = lower urinary symptoms due to benign prostatic hyperplasia; normal range. Treatment options include dietary modifica- @ = w“ hydralazine and metoprolol in selected patients with heart tions (phosphorus restriction) alone or in combination with ) failure; or metoprolol in patients with a recent myocardial the administration of phosphate binders. = Qa. infarction. None of these indications is present in this patient. KDIGO guidelines recommend against the use of acti- (=) amie vated vitamin D analogues such as calcitriol (Option A) in ma, non-dialysis-dependent patients with CKD to avoid the risk 2 J e Inthe absence of chronic kidney disease or heart fail- of calcium overload; therefore, calcitriol should be avoided @ wn ure, initial antihypertensive treatment with a thiazide in this non-dialysis-dependent patient. These agents are diuretic or calcium channel blocker is recommended routinely used in dialysis-dependent patients with end-stage in Black patients. kidney disease as CKD-MBD worsens.

Cardiology/American Heart Association guideline, four drug gut, contributing to hypocalcemia. Hypocalcemia is a potent classes (thiazide diuretics, CCBs, ACE inhibitors, or ARBs) stimulus for further increases in PTH levels. Increased PTH lower BP and reduce cardiovascular or renal outcomes. Except levels result in reduced calcium excretion, increased calcium for the combination of ACE inhibitors and ARBs, regimens absorption from the gut, increased phosphorus excretion by containing a combination of these classes are reasonable to the kidneys, and activation of osteoclast bone resorption. As achieve the BP target. Furthermore, the combination of an CKD progresses, the kidney is unable to compensate for the ACE inhibitor or ARB with a CCB or thiazide diuretic produces increased release of phosphorus from bone, and phosphorus similar BP lowering in Black patients as in those of other racial levels rise. Disordered calcium and phosphate metabolism or ethnic groups. lead to several adverse pathologic effects, including vascular Doxazosin, hydralazine, and metoprolol (Options B-D) are calcification, increased risk for cardiovascular events, and not recommended drugs for either initial therapy or as add-on the altered-bone physiology of renal osteodystrophy. The 2017 therapy in patients with hypertension, regardless of race or Kidney Disease: Improving Global Outcomes (KDIGO) guide- cod ethnicity, without the presence of compelling indications. Dox- lines recommend that, in patients with CKD stages G3a to —J “ azosin might be considered in male patients with bothersome GS, elevated phosphorus levels should be lowered toward the = lower urinary symptoms due to benign prostatic hyperplasia; normal range. Treatment options include dietary modifica- @ = w“ hydralazine and metoprolol in selected patients with heart tions (phosphorus restriction) alone or in combination with ) failure; or metoprolol in patients with a recent myocardial the administration of phosphate binders. = Qa. infarction. None of these indications is present in this patient. KDIGO guidelines recommend against the use of acti- (=) amie vated vitamin D analogues such as calcitriol (Option A) in ma, non-dialysis-dependent patients with CKD to avoid the risk 2 J e Inthe absence of chronic kidney disease or heart fail- of calcium overload; therefore, calcitriol should be avoided @ wn ure, initial antihypertensive treatment with a thiazide in this non-dialysis-dependent patient. These agents are diuretic or calcium channel blocker is recommended routinely used in dialysis-dependent patients with end-stage in Black patients. kidney disease as CKD-MBD worsens. e Except for the combination of ACE inhibitors and For patients who remain hyperphosphatemic following

Cardiology/American Heart Association guideline, four drug gut, contributing to hypocalcemia. Hypocalcemia is a potent classes (thiazide diuretics, CCBs, ACE inhibitors, or ARBs) stimulus for further increases in PTH levels. Increased PTH lower BP and reduce cardiovascular or renal outcomes. Except levels result in reduced calcium excretion, increased calcium for the combination of ACE inhibitors and ARBs, regimens absorption from the gut, increased phosphorus excretion by containing a combination of these classes are reasonable to the kidneys, and activation of osteoclast bone resorption. As achieve the BP target. Furthermore, the combination of an CKD progresses, the kidney is unable to compensate for the ACE inhibitor or ARB with a CCB or thiazide diuretic produces increased release of phosphorus from bone, and phosphorus similar BP lowering in Black patients as in those of other racial levels rise. Disordered calcium and phosphate metabolism or ethnic groups. lead to several adverse pathologic effects, including vascular Doxazosin, hydralazine, and metoprolol (Options B-D) are calcification, increased risk for cardiovascular events, and not recommended drugs for either initial therapy or as add-on the altered-bone physiology of renal osteodystrophy. The 2017 therapy in patients with hypertension, regardless of race or Kidney Disease: Improving Global Outcomes (KDIGO) guide- cod ethnicity, without the presence of compelling indications. Dox- lines recommend that, in patients with CKD stages G3a to —J “ azosin might be considered in male patients with bothersome GS, elevated phosphorus levels should be lowered toward the = lower urinary symptoms due to benign prostatic hyperplasia; normal range. Treatment options include dietary modifica- @ = w“ hydralazine and metoprolol in selected patients with heart tions (phosphorus restriction) alone or in combination with ) failure; or metoprolol in patients with a recent myocardial the administration of phosphate binders. = Qa. infarction. None of these indications is present in this patient. KDIGO guidelines recommend against the use of acti- (=) amie vated vitamin D analogues such as calcitriol (Option A) in ma, non-dialysis-dependent patients with CKD to avoid the risk 2 J e Inthe absence of chronic kidney disease or heart fail- of calcium overload; therefore, calcitriol should be avoided @ wn ure, initial antihypertensive treatment with a thiazide in this non-dialysis-dependent patient. These agents are diuretic or calcium channel blocker is recommended routinely used in dialysis-dependent patients with end-stage in Black patients. kidney disease as CKD-MBD worsens. e Except for the combination of ACE inhibitors and For patients who remain hyperphosphatemic following angiotensin receptor blockers (ARBs), regimens con- dietary optimization, the next step is addition of a phos- phate binder. The choice of a phosphate binder, calcium- or taining a combination of thiazide diuretics, calcium non-calcium-—based, must be individualized for each patient. channel blockers, ACE inhibitors, and ARBs are pre- Calcium-based binders include calcium carbonate and cal- ferred to achieve blood pressure goals in patients cium acetate (Option B); non-calcium-based binders include requiring dual antihypertensive therapy. sevelamer (Option E) and lanthanum. However, data are lack- ing to guide clinicians in choosing calcium-based binders. Bibliography Cinacalcet (Option C), a calcimimetic that decreases Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, PTH levels, is FDA approved for use in patients who are detection, evaluation, and management of high blood pressure in adults: undergoing dialysis but not for use in patients with CKD. a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016 /j.jacc.2017.11.006 e In patients with chronic kidney disease and hyper- phosphatemia, the initial step in management is a low Item 23 Answer: D phosphate diet. Educational Objective: Manage hyperphosphatemia in ¢ In patients with chronic kidney disease who remain chronic kidney disease-mineral and bone disorder. hyperphosphatemic following dietary optimization, The most appropriate management is dietary restriction of the next step is addition of a phosphate binder. phosphorus through a low phosphate diet (Option D). As kidney function declines, the normal homeostasis of calcium Bibliography and phosphorus levels by the kidney becomes compromised, Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update resulting in alterations in bone mineralization. The term Work Group. KDIGO 2017 clinical practice guideline update for the diag- nosis, evaluation, prevention, and treatment of chronic kidney disease- chronic kidney disease-mineral and bone disorder (CKD- mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1-59. MBD) encompasses these changes. Parathyroid hormone (PTH) is the most important regulator of calcium and phos- phorus concentrations. PTH stimulates osteoclasts to resorb Item 24 Answer: C bone, stimulates hydroxylation of 25-hydroxyvitamin D in the Educational Objective: Diagnose chronic interstitial kidneys, and stimulates tubular reabsorption of calcium and nephritis in agricultural communities. induces renal phosphorus excretion. As CKD progresses, ris- ing fibroblast growth factor 23 levels inhibit the conversion of Chronic interstitial nephritis (Option C) is the most likely 25-hydroxyvitaminD to 1,25-dihydroxyvitamin D, resulting in diagnosis. Chronic interstitial nephritis in agricultural com- lower intestinal absorption of calcium and phosphorus in the munities (CINAC; also known as Mesoamerican nephropathy)

angiotensin receptor blockers (ARBs), regimens con- dietary optimization, the next step is addition of a phos- phate binder. The choice of a phosphate binder, calcium- or taining a combination of thiazide diuretics, calcium non-calcium-—based, must be individualized for each patient. channel blockers, ACE inhibitors, and ARBs are pre- Calcium-based binders include calcium carbonate and cal- ferred to achieve blood pressure goals in patients cium acetate (Option B); non-calcium-based binders include requiring dual antihypertensive therapy. sevelamer (Option E) and lanthanum. However, data are lack- ing to guide clinicians in choosing calcium-based binders. Bibliography Cinacalcet (Option C), a calcimimetic that decreases Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, PTH levels, is FDA approved for use in patients who are detection, evaluation, and management of high blood pressure in adults: undergoing dialysis but not for use in patients with CKD. a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016 /j.jacc.2017.11.006 e In patients with chronic kidney disease and hyper- phosphatemia, the initial step in management is a low Item 23 Answer: D phosphate diet. Educational Objective: Manage hyperphosphatemia in ¢ In patients with chronic kidney disease who remain chronic kidney disease-mineral and bone disorder. hyperphosphatemic following dietary optimization, The most appropriate management is dietary restriction of the next step is addition of a phosphate binder. phosphorus through a low phosphate diet (Option D). As kidney function declines, the normal homeostasis of calcium Bibliography and phosphorus levels by the kidney becomes compromised, Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update resulting in alterations in bone mineralization. The term Work Group. KDIGO 2017 clinical practice guideline update for the diag- nosis, evaluation, prevention, and treatment of chronic kidney disease- chronic kidney disease-mineral and bone disorder (CKD- mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1-59. MBD) encompasses these changes. Parathyroid hormone (PTH) is the most important regulator of calcium and phos- phorus concentrations. PTH stimulates osteoclasts to resorb Item 24 Answer: C bone, stimulates hydroxylation of 25-hydroxyvitamin D in the Educational Objective: Diagnose chronic interstitial kidneys, and stimulates tubular reabsorption of calcium and nephritis in agricultural communities. induces renal phosphorus excretion. As CKD progresses, ris- ing fibroblast growth factor 23 levels inhibit the conversion of Chronic interstitial nephritis (Option C) is the most likely 25-hydroxyvitaminD to 1,25-dihydroxyvitamin D, resulting in diagnosis. Chronic interstitial nephritis in agricultural com- lower intestinal absorption of calcium and phosphorus in the munities (CINAC; also known as Mesoamerican nephropathy) 132

and AnswersCritiques is an emerging public health problem in many Central Amer- increase in the serum creatinine level of at least 0.3 mg/dL ican and Asian countries. It is observed most commonly in (26.5 umol/L) and/or 250% from baseline within 48 hours; young- to middle-aged male migratory agricultural workers bland urinalysis; and normal findings on kidney ultrasound. and often progresses to end-stage kidney disease. This patient It is also supported by a lack of improvement in kidney func- has many findings associated with chronic tubulointerstitial tion after withdrawal of diuretics and 2 days of volume expan kidney disease. He is hypertensive and has a normal anion gap sion with intravenous albumin. Often, patients also have low metabolic acidosis. Furthermore, his urinalysis demonstrates urine sodium, low fractional excretion of sodium, and oligu- pyuria and low-grade proteinuria, and his kidney ultrasound ria. Type 2 HRS is defined as a more gradual decline in kidney shows nonspecific chronic kidney injury changes (increased function associated with refractory ascites. General manage- cortical echogenicity and mild thinning). These findings, in ment includes discontinuing diuretics, restricting sodium. the context of a patient who is a migratory agricultural worker restricting water in hyponatremic patients, and searching for in Central America, suggest that he has developed CINAC. precipitating factors. Therapeutic interventions include treat- Kidney biopsy may establish a definitive diagnosis. ment with vasoconstrictors and albumin. wn a Acute interstitial nephritis (Option A) is characterized Patients with HRS have an overall poor prognosis with- Z

is an emerging public health problem in many Central Amer- increase in the serum creatinine level of at least 0.3 mg/dL ican and Asian countries. It is observed most commonly in (26.5 umol/L) and/or 250% from baseline within 48 hours; young- to middle-aged male migratory agricultural workers bland urinalysis; and normal findings on kidney ultrasound. and often progresses to end-stage kidney disease. This patient It is also supported by a lack of improvement in kidney func- has many findings associated with chronic tubulointerstitial tion after withdrawal of diuretics and 2 days of volume expan kidney disease. He is hypertensive and has a normal anion gap sion with intravenous albumin. Often, patients also have low metabolic acidosis. Furthermore, his urinalysis demonstrates urine sodium, low fractional excretion of sodium, and oligu- pyuria and low-grade proteinuria, and his kidney ultrasound ria. Type 2 HRS is defined as a more gradual decline in kidney shows nonspecific chronic kidney injury changes (increased function associated with refractory ascites. General manage- cortical echogenicity and mild thinning). These findings, in ment includes discontinuing diuretics, restricting sodium. the context of a patient who is a migratory agricultural worker restricting water in hyponatremic patients, and searching for in Central America, suggest that he has developed CINAC. precipitating factors. Therapeutic interventions include treat- Kidney biopsy may establish a definitive diagnosis. ment with vasoconstrictors and albumin. wn a Acute interstitial nephritis (Option A) is characterized Patients with HRS have an overall poor prognosis with- Z by urine sediment containing leukocytes and leukocyte out liver transplantation. Hemodialysis (Option A) is typi- = cally not the best therapeutic option unless the patient is a = casts, unlike this patient’s relatively bland urine sediment. oO Although patients with acute bacterial infection may liver transplant candidate. <s = occasionally present with acute tubular necrosis (Option B), Treatment of hepatorenal syndrome may also include c

by urine sediment containing leukocytes and leukocyte out liver transplantation. Hemodialysis (Option A) is typi- = cally not the best therapeutic option unless the patient is a = casts, unlike this patient’s relatively bland urine sediment. oO Although patients with acute bacterial infection may liver transplant candidate. <s = occasionally present with acute tubular necrosis (Option B), Treatment of hepatorenal syndrome may also include c these patients typically have features of a systemic inflam- the vasoconstrictors midodrine and octreotide (Option C) 2 o matory response syndrome at the time of presentation and along with intravenous albumin to raise mean arterial pres = nn urine sediment showing granular casts. sure and improve kidney perfusion. However, midodrine = IgA nephropathy (Option D) is a chronic glomerular and octreotide are not necessary in a patient such as this one <=

these patients typically have features of a systemic inflam- the vasoconstrictors midodrine and octreotide (Option C) 2 o matory response syndrome at the time of presentation and along with intravenous albumin to raise mean arterial pres = nn urine sediment showing granular casts. sure and improve kidney perfusion. However, midodrine = IgA nephropathy (Option D) is a chronic glomerular and octreotide are not necessary in a patient such as this one <= disease typically characterized by microhematuria and occa- who is receiving intravenous norepinephrine. sional episodes of gross hematuria. This patient has a chronic Although transjugular intrahepatic portosystemic shunt tubulointerstitial disorder, not a glomerular disorder. (Option D) is an effective therapy for some cases of refrac- Infection-related glomerulonephritis (Option E), tory HRS, it is an invasive therapy with numerous potential which may be seen concurrent with or following cellulitis, complications that should not preempt the administration is accompanied by erythrocytes and erythrocyte casts in the of albumin. urine sediment and often resolves after the acute infection resolves. ¢ Type 1 hepatorenal syndrome is characterized by an increase in the serum creatinine level of at least e Chronic interstitial nephritis in agricultural communities 0.3 mg/dL (26.5 pmol/L) and/or >50% from baseline is most commonly observed in young- to middle-aged within 48 hours; bland urinalysis; and normal findings male agricultural workers and often progresses to end- on kidney ultrasound. stage kidney disease. e Treatment of type 1 hepatorenal syndrome includes e Patients with chronic interstitial nephritis in agricul- vasoconstrictors and intravenous albumin. tural communities may be hypertensive, and urinalysis may be normal or demonstrate pyuria and low-grade Bibliography proteinuria. Best LM, Freeman SC, Sutton AJ, et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev. 2019;9:CD013103. [PMID: 31513287] Bibliography doi:10.1002/14651858.CD013103.pub2

disease typically characterized by microhematuria and occa- who is receiving intravenous norepinephrine. sional episodes of gross hematuria. This patient has a chronic Although transjugular intrahepatic portosystemic shunt tubulointerstitial disorder, not a glomerular disorder. (Option D) is an effective therapy for some cases of refrac- Infection-related glomerulonephritis (Option E), tory HRS, it is an invasive therapy with numerous potential which may be seen concurrent with or following cellulitis, complications that should not preempt the administration is accompanied by erythrocytes and erythrocyte casts in the of albumin. urine sediment and often resolves after the acute infection resolves. ¢ Type 1 hepatorenal syndrome is characterized by an increase in the serum creatinine level of at least e Chronic interstitial nephritis in agricultural communities 0.3 mg/dL (26.5 pmol/L) and/or >50% from baseline is most commonly observed in young- to middle-aged within 48 hours; bland urinalysis; and normal findings male agricultural workers and often progresses to end- on kidney ultrasound. stage kidney disease. e Treatment of type 1 hepatorenal syndrome includes e Patients with chronic interstitial nephritis in agricul- vasoconstrictors and intravenous albumin. tural communities may be hypertensive, and urinalysis may be normal or demonstrate pyuria and low-grade Bibliography proteinuria. Best LM, Freeman SC, Sutton AJ, et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev. 2019;9:CD013103. [PMID: 31513287] Bibliography doi:10.1002/14651858.CD013103.pub2 Orantes-Navarro CM, Herrera-Valdés R, Almaguer-Lopez M, et al. Toward a comprehensive hypothesis of chronic interstitial nephritis in agricultural communities. Adv Chronic Kidney Dis. 2017;24:101-106. [PMID: 28284375] doi:10.1053/j.ackd.2017.01.001 Item 26 Answer: D Educational Objective: Screen for skin cancer ina kidney transplant recipient. Item 25 Answer: B The most appropriate screening test to perform next is a skin Educational Objective: Treat hepatorenal syndrome. examination (Option D). This patient, who is at increased The most appropriate additional treatment is intravenous risk for multiple types of skin cancer, should be referred to a albumin (Option B). This patient exhibits acute kidney injury dermatologist or a clinician with special expertise for annual (AKI) in the context of advanced cirrhosis. At this stage in screening; screening frequency is increased for patients who her hospitalization, it is uncertain if she could have prerenal have a history of skin cancer. Kidney transplant recipients AKI, acute tubular necrosis, or hepatorenal syndrome (HRS). are at increased risk for various complications due to their Type 1 HRS is a clinical diagnosis made after exclusion of original underlying end-stage kidney disease and the use other causes of kidney dysfunction. It is characterized by an of chronic immunosuppressive medications, which may be

Orantes-Navarro CM, Herrera-Valdés R, Almaguer-Lopez M, et al. Toward a comprehensive hypothesis of chronic interstitial nephritis in agricultural communities. Adv Chronic Kidney Dis. 2017;24:101-106. [PMID: 28284375] doi:10.1053/j.ackd.2017.01.001 Item 26 Answer: D Educational Objective: Screen for skin cancer ina kidney transplant recipient. Item 25 Answer: B The most appropriate screening test to perform next is a skin Educational Objective: Treat hepatorenal syndrome. examination (Option D). This patient, who is at increased The most appropriate additional treatment is intravenous risk for multiple types of skin cancer, should be referred to a albumin (Option B). This patient exhibits acute kidney injury dermatologist or a clinician with special expertise for annual (AKI) in the context of advanced cirrhosis. At this stage in screening; screening frequency is increased for patients who her hospitalization, it is uncertain if she could have prerenal have a history of skin cancer. Kidney transplant recipients AKI, acute tubular necrosis, or hepatorenal syndrome (HRS). are at increased risk for various complications due to their Type 1 HRS is a clinical diagnosis made after exclusion of original underlying end-stage kidney disease and the use other causes of kidney dysfunction. It is characterized by an of chronic immunosuppressive medications, which may be 133

Answers and Critiques related to risks for altered immune surveillance or idiosyn- patient. In patients with proteinuria, treatment with ACE cratic medication side effects. Kidney transplant recipients inhibitors or ARBs lowers intraglomerular pressure result- are at increased risk for several other malignancies, includ- ing in decreased protein excretion and often slows the rate ing renal cell carcinoma, colon cancer, lung cancer, thyroid of declining kidney function. Acute decline in glomerular cancer, anogenital cancers, and posttransplant lymphoprolif- filtration rate and hyperkalemia are well-recognized poten- erative disease. These patients are also at increased risk for car- tial adverse effects of these drugs, mandating monitoring diovascular disease, and those treated with glucocorticoids, of serum creatinine and potassium levels. Antiproteinuric calcineurin inhibitors, and mTOR inhibitors are at increased therapy is usually coupled with lipid-lowering therapy and risk for new-onset diabetes after transplant (NODAT). fish oil, although the efficacy of the latter two as specific The U.S. Preventive Services Task Force (USPSTF) recom- IgAN therapies is unproven. mends screening for colorectal cancer in asymptomatic adults Mycophenolate mofetil (Option B) is reserved as a second- aged 50 to 75 years. The USPSTF supports using the test that or third-line therapy for patients with IgAN who decline > is most likely to result in completion of screening. Options despite glucocorticoid or other immunosuppression. This = wn include colonoscopy (Option A), flexible sigmoidoscopy, CT treatment has only shown benefit in patients of Asian descent. = colonography, stool-based testing, and combination of stool- Despite its purported anti-inflammatory properties, the oO = wn based testing and flexible sigmoidoscopy. This patient should benefit of treating IgAN with omega-3 fatty acids (fish oil) 33) be screened for colon cancer beginning at 50 years of age. (Option C) is unclear. Because of its safety, it can be used —] Q A low-dose chest CT (Option B) to screen for lung cancer in conjunction with other therapies but should not be the (se) = is not indicated. Although patients on immunosuppressive exclusive treatment of IgAN. =. medications are at increased risk for various cancers, screen- Immunosuppressive therapy, such as prednisone 2 = ing for non-skin cancers should follow guidelines for the gen- (Option D), would not be used for this patient. Although © 7) eral population. The criteria for screening include those who two thirds of patients with IgAN will have progressive loss are aged 55 to 74-80 years (guidelines differ on ages to discon- of kidney function, the use of immunosuppressive ther- tinue screening), have at least a 30-pack-year smoking history, apy remains controversial. Small studies have shown that and are current smokers or have quit within the last 15 years. a 6-month course of prednisone reduces proteinuria and Kidney transplant recipients are at risk for NODAT. Post- slows decline in glomerular filtration rate in patients with transplant fasting glucose and symptoms should be moni- IgAN and >1000 mg/24 h proteinuria despite maximal tored. Fasting glucose is monitored more frequently in the therapy with an ACE inhibitor or ARB. However, two large first year after transplant and then annually in the absence of randomized controlled trials (STOP-IgAN and TESTING) symptoms to suggest hyperglycemia. The diagnosis of NODAT called into question this management. The STOP-IgAN study is made based on the same criteria as that for the general showed no difference in changes in kidney function between population. An oral glucose tolerance test (Option C) is not those patients with IgAN treated with or without immuno- indicated for this patient with a normal fasting blood glucose. suppression over a 3-year period. The TESTING study was terminated early due to significantly higher rates of adverse events in patients with IgAN who were treated with pred- e Kidney transplant recipients are at increased risk for nisone. As a result, treatment efficacy could not be deter- multiple types of skin cancer and should undergo mined. Because this patient has not yet been treated with an annual skin examination. ACE inhibitor or ARB, consideration of immunosuppressive

related to risks for altered immune surveillance or idiosyn- patient. In patients with proteinuria, treatment with ACE cratic medication side effects. Kidney transplant recipients inhibitors or ARBs lowers intraglomerular pressure result- are at increased risk for several other malignancies, includ- ing in decreased protein excretion and often slows the rate ing renal cell carcinoma, colon cancer, lung cancer, thyroid of declining kidney function. Acute decline in glomerular cancer, anogenital cancers, and posttransplant lymphoprolif- filtration rate and hyperkalemia are well-recognized poten- erative disease. These patients are also at increased risk for car- tial adverse effects of these drugs, mandating monitoring diovascular disease, and those treated with glucocorticoids, of serum creatinine and potassium levels. Antiproteinuric calcineurin inhibitors, and mTOR inhibitors are at increased therapy is usually coupled with lipid-lowering therapy and risk for new-onset diabetes after transplant (NODAT). fish oil, although the efficacy of the latter two as specific The U.S. Preventive Services Task Force (USPSTF) recom- IgAN therapies is unproven. mends screening for colorectal cancer in asymptomatic adults Mycophenolate mofetil (Option B) is reserved as a second- aged 50 to 75 years. The USPSTF supports using the test that or third-line therapy for patients with IgAN who decline > is most likely to result in completion of screening. Options despite glucocorticoid or other immunosuppression. This = wn include colonoscopy (Option A), flexible sigmoidoscopy, CT treatment has only shown benefit in patients of Asian descent. = colonography, stool-based testing, and combination of stool- Despite its purported anti-inflammatory properties, the oO = wn based testing and flexible sigmoidoscopy. This patient should benefit of treating IgAN with omega-3 fatty acids (fish oil) 33) be screened for colon cancer beginning at 50 years of age. (Option C) is unclear. Because of its safety, it can be used —] Q A low-dose chest CT (Option B) to screen for lung cancer in conjunction with other therapies but should not be the (se) = is not indicated. Although patients on immunosuppressive exclusive treatment of IgAN. =. medications are at increased risk for various cancers, screen- Immunosuppressive therapy, such as prednisone 2 = ing for non-skin cancers should follow guidelines for the gen- (Option D), would not be used for this patient. Although © 7) eral population. The criteria for screening include those who two thirds of patients with IgAN will have progressive loss are aged 55 to 74-80 years (guidelines differ on ages to discon- of kidney function, the use of immunosuppressive ther- tinue screening), have at least a 30-pack-year smoking history, apy remains controversial. Small studies have shown that and are current smokers or have quit within the last 15 years. a 6-month course of prednisone reduces proteinuria and Kidney transplant recipients are at risk for NODAT. Post- slows decline in glomerular filtration rate in patients with transplant fasting glucose and symptoms should be moni- IgAN and >1000 mg/24 h proteinuria despite maximal tored. Fasting glucose is monitored more frequently in the therapy with an ACE inhibitor or ARB. However, two large first year after transplant and then annually in the absence of randomized controlled trials (STOP-IgAN and TESTING) symptoms to suggest hyperglycemia. The diagnosis of NODAT called into question this management. The STOP-IgAN study is made based on the same criteria as that for the general showed no difference in changes in kidney function between population. An oral glucose tolerance test (Option C) is not those patients with IgAN treated with or without immuno- indicated for this patient with a normal fasting blood glucose. suppression over a 3-year period. The TESTING study was terminated early due to significantly higher rates of adverse events in patients with IgAN who were treated with pred- e Kidney transplant recipients are at increased risk for nisone. As a result, treatment efficacy could not be deter- multiple types of skin cancer and should undergo mined. Because this patient has not yet been treated with an annual skin examination. ACE inhibitor or ARB, consideration of immunosuppressive e Although patients on immunosuppressive medications therapy with prednisone is premature.

related to risks for altered immune surveillance or idiosyn- patient. In patients with proteinuria, treatment with ACE cratic medication side effects. Kidney transplant recipients inhibitors or ARBs lowers intraglomerular pressure result- are at increased risk for several other malignancies, includ- ing in decreased protein excretion and often slows the rate ing renal cell carcinoma, colon cancer, lung cancer, thyroid of declining kidney function. Acute decline in glomerular cancer, anogenital cancers, and posttransplant lymphoprolif- filtration rate and hyperkalemia are well-recognized poten- erative disease. These patients are also at increased risk for car- tial adverse effects of these drugs, mandating monitoring diovascular disease, and those treated with glucocorticoids, of serum creatinine and potassium levels. Antiproteinuric calcineurin inhibitors, and mTOR inhibitors are at increased therapy is usually coupled with lipid-lowering therapy and risk for new-onset diabetes after transplant (NODAT). fish oil, although the efficacy of the latter two as specific The U.S. Preventive Services Task Force (USPSTF) recom- IgAN therapies is unproven. mends screening for colorectal cancer in asymptomatic adults Mycophenolate mofetil (Option B) is reserved as a second- aged 50 to 75 years. The USPSTF supports using the test that or third-line therapy for patients with IgAN who decline > is most likely to result in completion of screening. Options despite glucocorticoid or other immunosuppression. This = wn include colonoscopy (Option A), flexible sigmoidoscopy, CT treatment has only shown benefit in patients of Asian descent. = colonography, stool-based testing, and combination of stool- Despite its purported anti-inflammatory properties, the oO = wn based testing and flexible sigmoidoscopy. This patient should benefit of treating IgAN with omega-3 fatty acids (fish oil) 33) be screened for colon cancer beginning at 50 years of age. (Option C) is unclear. Because of its safety, it can be used —] Q A low-dose chest CT (Option B) to screen for lung cancer in conjunction with other therapies but should not be the (se) = is not indicated. Although patients on immunosuppressive exclusive treatment of IgAN. =. medications are at increased risk for various cancers, screen- Immunosuppressive therapy, such as prednisone 2 = ing for non-skin cancers should follow guidelines for the gen- (Option D), would not be used for this patient. Although © 7) eral population. The criteria for screening include those who two thirds of patients with IgAN will have progressive loss are aged 55 to 74-80 years (guidelines differ on ages to discon- of kidney function, the use of immunosuppressive ther- tinue screening), have at least a 30-pack-year smoking history, apy remains controversial. Small studies have shown that and are current smokers or have quit within the last 15 years. a 6-month course of prednisone reduces proteinuria and Kidney transplant recipients are at risk for NODAT. Post- slows decline in glomerular filtration rate in patients with transplant fasting glucose and symptoms should be moni- IgAN and >1000 mg/24 h proteinuria despite maximal tored. Fasting glucose is monitored more frequently in the therapy with an ACE inhibitor or ARB. However, two large first year after transplant and then annually in the absence of randomized controlled trials (STOP-IgAN and TESTING) symptoms to suggest hyperglycemia. The diagnosis of NODAT called into question this management. The STOP-IgAN study is made based on the same criteria as that for the general showed no difference in changes in kidney function between population. An oral glucose tolerance test (Option C) is not those patients with IgAN treated with or without immuno- indicated for this patient with a normal fasting blood glucose. suppression over a 3-year period. The TESTING study was terminated early due to significantly higher rates of adverse events in patients with IgAN who were treated with pred- e Kidney transplant recipients are at increased risk for nisone. As a result, treatment efficacy could not be deter- multiple types of skin cancer and should undergo mined. Because this patient has not yet been treated with an annual skin examination. ACE inhibitor or ARB, consideration of immunosuppressive e Although patients on immunosuppressive medications therapy with prednisone is premature. are at increased risk for various cancers, screening for non-skin cancers should follow guidelines for the e First-line therapy for IgA nephropathy is either an general population. ACE inhibitor or an angiotensin receptor blocker.

are at increased risk for various cancers, screening for non-skin cancers should follow guidelines for the e First-line therapy for IgA nephropathy is either an general population. ACE inhibitor or an angiotensin receptor blocker. e Treatment of IgA nephropathy with high-dose gluco- Bibliography Voora S, Adey DB. Management of kidney transplant recipients by general corticoids is associated with an increased risk for nephrologists: core curriculum 2019. Am J Kidney Dis. 2019;73:866-879. adverse events and may not improve kidney function. [PMID: 30981567] doi:10.1053/j.ajkd.2019.01.031 Bibliography Item 27 Answer: A Barratt J, Tang SCW. Treatment of IgA nephropathy: evolution over half a century. Semin Nephrol. 2018;38:531-540. [PMID: 30177025] doi:10.1016 /j. Educational Objective: Treat IgA nephropathy with semnephrol.2018.05.023 blockade of the renin-angiotensin system. First-line therapy for IgA nephropathy (IgAN) is initiation Item 28 Answer: C of antiproteinuric therapy with blockade of the renin- Educational Objective: Treat acute hyponatremia. angiotensin system using either an ACE inhibitor, such as lisinopril (Option A), or an angiotensin receptor blocker The most appropriate management is a 100-mL bolus of (ARB) and is the most appropriate management for this 3% saline (Option C). Symptoms caused by hyponatremia 134

Answers and Critiques depend on both the rapidity and degree of decline in Item 29 Answer: D serum sodium. A sudden drop in serum sodium causes Educational Objective: Evaluate chronic kidney water to move into the brain, producing cerebral edema disease. and possibly causing headaches, seizures, or death. Hypo- natremia has been reported in inexperienced marathon The most appropriate test to help diagnose the cause and runners who overhydrate. A systematic study of hypo- assess the prognosis of this patient’s chronic kidney disease natremia in runners finishing a marathon revealed that (CKD) is a spot urine albumin-creatinine ratio (Option D). 13% had a serum sodium concentration of <135 mEq/L CKD is defined as abnormal kidney structure or function (135 mmol/L) and 0.6% had critical hyponatremia of <120 present for >3 months. CKD is stratified into stages 1 to 5 mEq/L (120 mmol/L). Hyponatremia was associated with based on the level of estimated glomerular filtration rate consumption of more than 3 liters of fluids during the (eGFR). Because albuminuria is associated with increased race, consumption of fluids every mile, and a racing time renal and cardiovascular morbidity and mortality, eGFR- of more than 4 hours, which is a possible indication of less based kidney stages are modified by the degree of albumin- n a training. Female runners remain a readily identifiable risk uria. This dual eGFR and albuminuria-staging matrix pro- oI

of more than 4 hours, which is a possible indication of less based kidney stages are modified by the degree of albumin- n a training. Female runners remain a readily identifiable risk uria. This dual eGFR and albuminuria-staging matrix pro- oI group in many studies, but this may represent the impact vides a means for predicting which patients are at highest = risk for developing end-stage kidney disease. This patient 1 of body size and longer racing time rather than the sex of oO the athlete. The other major factor causing hyponatremia has CKD confirmed by a persistently low eGFR for at least sc = in endurance athletes is persistent secretion of antidiuretic 6 months. A spot urine albumin-creatinine ratio should ©

group in many studies, but this may represent the impact vides a means for predicting which patients are at highest = risk for developing end-stage kidney disease. This patient 1 of body size and longer racing time rather than the sex of oO the athlete. The other major factor causing hyponatremia has CKD confirmed by a persistently low eGFR for at least sc = in endurance athletes is persistent secretion of antidiuretic 6 months. A spot urine albumin-creatinine ratio should © hormone (ADH). Because hyponatremia is not uncommon be obtained to determine the degree of proteinuria. In wn Tees o with extreme exercise and overhydration, it is important addition to prognostication, this test will help categorize = that medical personnel are able to measure sodium rapidly. his CKD as nephrotic or non-nephrotic, which will inform ” = If the patient’s sodium cannot be measured, treatment diagnostic testing. <r should be held until the patient can be transported to a Controlling hyperglycemia in patients with diabetes facility where sodium measurements can be made. Indi- mellitus will slow the progression of CKD. Although a hemo-

hormone (ADH). Because hyponatremia is not uncommon be obtained to determine the degree of proteinuria. In wn Tees o with extreme exercise and overhydration, it is important addition to prognostication, this test will help categorize = that medical personnel are able to measure sodium rapidly. his CKD as nephrotic or non-nephrotic, which will inform ” = If the patient’s sodium cannot be measured, treatment diagnostic testing. <r should be held until the patient can be transported to a Controlling hyperglycemia in patients with diabetes facility where sodium measurements can be made. Indi- mellitus will slow the progression of CKD. Although a hemo- viduals with severe symptoms (e.g., confusion, coma, sei- globin A,. measurement (Option A) is important in the zures) secondary to acute hyponatremia should be treated management of diabetes, it is not the most appropriate test with a 100-mL bolus of 3% saline. If symptoms do not to determine the cause and prognosis of CKD. improve and the sodium remains low, an additional bolus Kidney biopsy (Option B) is used to determine the can be given. cause of CKD when a glomerulonephritis or unexplained

with a 100-mL bolus of 3% saline. If symptoms do not to determine the cause and prognosis of CKD. improve and the sodium remains low, an additional bolus Kidney biopsy (Option B) is used to determine the can be given. cause of CKD when a glomerulonephritis or unexplained Although fluid restriction (Option A) may allow for tubulointerstitial disease is likely. Kidney biopsy is not correction of serum sodium in persons with minimal symp- indicated in the presence of shrunken kidneys (<9 cm), toms, it should never be the sole treatment when severe which generally indicate chronic irreversible disease. Con- symptoms such as confusion are present, as they are in this sideration of a kidney biopsy is premature for this patient, patient. pending results of kidney ultrasonography, urine albu- Intravenous 0.9% saline (Option B) should not min-creatinine ratio, and ophthalmology examination. If be administered in this patient. If her ADH levels are retinopathy is confirmed by a dilated retinal examination extremely elevated, her urine osmolality will exceed and the patient has albuminuria, the most likely diagno- the osmolality of normal saline. Intravenous 0.9% saline sis in this patient with long-standing diabetes is diabetic

be administered in this patient. If her ADH levels are retinopathy is confirmed by a dilated retinal examination extremely elevated, her urine osmolality will exceed and the patient has albuminuria, the most likely diagno- the osmolality of normal saline. Intravenous 0.9% saline sis in this patient with long-standing diabetes is diabetic could potentially lower the patient’s sodium further. kidney disease. The use of 0.9% saline should be limited to those Serum parathyroid hormone (Option C), calcium, phos- patients with evidence of volume depletion and minimal phorus, and 25-hydroxyvitamin D levels are indicated for symptoms. management of CKD-mineral and bone disorder. Although It is inappropriate to not treat this patient (Option D). these laboratory studies are indicated for all patients with This patient’s serum sodium is 130 mEq/L (130 mmol/L), and CKD, they are not used as tests to help determine the prog- serious neurologic symptoms may occur when the sodium nosis of CKD. decreases acutely to <132 mEq/L (132 mmol/L). Therefore, this patient needs prompt treatment. e Chronic kidney disease is defined as abnormal kidney structure or function present for >3 months. e Acute hyponatremia developing in less than 48 hours e In patients with chronic kidney disease, albuminuria can cause headaches, seizures, or death. is associated with increased renal and cardiovascular e Acute hyponatremia should be treated with a 100-mL morbidity and mortality. bolus of 3% saline.

could potentially lower the patient’s sodium further. kidney disease. The use of 0.9% saline should be limited to those Serum parathyroid hormone (Option C), calcium, phos- patients with evidence of volume depletion and minimal phorus, and 25-hydroxyvitamin D levels are indicated for symptoms. management of CKD-mineral and bone disorder. Although It is inappropriate to not treat this patient (Option D). these laboratory studies are indicated for all patients with This patient’s serum sodium is 130 mEq/L (130 mmol/L), and CKD, they are not used as tests to help determine the prog- serious neurologic symptoms may occur when the sodium nosis of CKD. decreases acutely to <132 mEq/L (132 mmol/L). Therefore, this patient needs prompt treatment. e Chronic kidney disease is defined as abnormal kidney structure or function present for >3 months. e Acute hyponatremia developing in less than 48 hours e In patients with chronic kidney disease, albuminuria can cause headaches, seizures, or death. is associated with increased renal and cardiovascular e Acute hyponatremia should be treated with a 100-mL morbidity and mortality. bolus of 3% saline. Bibliography Bibliography Hoorn EJ, Zietse R. Diagnosis and treatment of hyponatremia: compilation Chen TK, Knicely DH, Grams ME. Chronic kidney disease diagnosis and of the guidelines. J Am Soc Nephrol. 2017;28:1340-1349. [PMID: 28174217] management: a review. JAMA. 2019;322:1294-1304. [PMID: 31573641] doi:10.1681/ASN.2016101139 doi:10.1001/jama.2019.14745 135

Item 30 Answer: A Type 2 RTA involves a proximal tubular defect in reclaim- ing bicarbonate and is characterized by a normal anion Educational Objective: Treat a hypertensive emergency gap metabolic acidosis, hypokalemia, glycosuria (without with aortic dissection. hyperglycemia), low-molecular-weight proteinuria, and The most appropriate initial treatment is to administer intrave- renal phosphate wasting (known as Fanconi syndrome when nous (IV) esmolol (Option A). This patient has a hypertensive all features are present). Because distal urine acidification emergency with a type A aortic dissection involving the ascend remains intact, the urine pH is usually <5.5 without alkali ing aorta. For hypertensive emergency with evidence of end- therapy, and the urine anion gap ([Urine Sodium + Urine organ damage, blood pressure (BP) should be rapidly lowered Potassium] - Urine Chloride) would be negative, reflecting using IV short-acting agents. Esmolol is a B,-selective adrenergic increased excretion of acid in the form of ammonium and receptor blocker with a 1- to 2-minute onset of action. Esmolol chloride. This patient’s normal anion gap metabolic acidosis, can rapidly reduce heart rate and BP, thereby reducing aortic low urine pH, hypokalemia, and hypophosphatemia makes PI wall sheer stress and limiting the propagation of the dissection. type 2 RTA most likely. Type 2 RTA in this case is likely due = wn The 2017 American College of Cardiology/American Heart Asso to multiple myeloma-associated light chain proximal tub- = ciation BP guideline recommends that for adults with a compel- ulopathy. Multiple myeloma is suggested by the presence of oO = wn ling condition (such as aortic dissection, severe preeclampsia or anemia and high gamma globulin fraction (elevated total 35) eclampsia, or pheochromocytoma crisis), systolic BP should be protein and low albumin concentrations). = Qa. reduced to <140 mm Hg during the first hour and to <120 mm Bartter syndrome (Option A) can cause hypokalemia a Hg in aortic dissection. Referral for emergency surgery should and hypophosphatemia but is also associated with metabolic =s =. be considered in all patients with type A aortic dissection given alkalosis and most often presents in childhood. Liddle syn- <2 sa the very high mortality rate associated with this condition. drome (Option B) causes increased sodium reabsorption in oO wn Hydralazine (Option B) can increase myocardial con- the distal nephron with resulting hypertension, metabolic tractility and is not the first-line treatment in this case. alkalosis, and potassium wasting. This patient has a normal Treatment with an IV rapidly acting calcium channel anion gap metabolic acidosis, which excludes Bartter and blocker such as nicardipine (Option C) or with a vasodilator Liddle syndromes. such as nitroprusside (Option D) should not be initiated Type 1 (hypokalemic distal) RTA (Option C) is due to a before B-blockade. In the absence of B—blockade, vasodilator defect in urine acidification in the distal nephron. Because therapy induces reflex activation of the sympathetic nervous of the inability to excrete hydrogen ions, patients develop system, resulting in tachycardia and enhanced ventricular a metabolic acidosis with compensatory hyperchloremia, contraction, which increases aortic wall shear stress. Follow- resulting in a normal anion gap and the inability to acidify ing effective B-blockade, vasodilator therapy can be initiated urine below a pH of 6.0; this patient’s urine pH is 5.0. to reduce the systolic BP to <120 mm Hg. The urine anion gap is positive, reflecting decreased acid excretion in the form of ammonium and chloride. The same defects also cause potassium wasting, and the increased e Intravenous short-acting B,-selective adrenergic proximal resorption of citrate that occurs with metabolic receptor blockers are an initial first-line treatment to acidosis leads to hypocitraturia and increased risk for cal- rapidly lower blood pressure in patients with hyper- cium phosphate kidney stones and nephrocalcinosis. tensive emergency and aortic dissection. Type 4 (hyperkalemic distal) RTA (Option E) due to ¢ In adults with a compelling condition (such as aortic aldosterone deficiency or resistance is associated with a mild dissection, severe preeclampsia or eclampsia, or phe- normal anion gap metabolic acidosis and hyperkalemia,

Item 30 Answer: A Type 2 RTA involves a proximal tubular defect in reclaim- ing bicarbonate and is characterized by a normal anion Educational Objective: Treat a hypertensive emergency gap metabolic acidosis, hypokalemia, glycosuria (without with aortic dissection. hyperglycemia), low-molecular-weight proteinuria, and The most appropriate initial treatment is to administer intrave- renal phosphate wasting (known as Fanconi syndrome when nous (IV) esmolol (Option A). This patient has a hypertensive all features are present). Because distal urine acidification emergency with a type A aortic dissection involving the ascend remains intact, the urine pH is usually <5.5 without alkali ing aorta. For hypertensive emergency with evidence of end- therapy, and the urine anion gap ([Urine Sodium + Urine organ damage, blood pressure (BP) should be rapidly lowered Potassium] - Urine Chloride) would be negative, reflecting using IV short-acting agents. Esmolol is a B,-selective adrenergic increased excretion of acid in the form of ammonium and receptor blocker with a 1- to 2-minute onset of action. Esmolol chloride. This patient’s normal anion gap metabolic acidosis, can rapidly reduce heart rate and BP, thereby reducing aortic low urine pH, hypokalemia, and hypophosphatemia makes PI wall sheer stress and limiting the propagation of the dissection. type 2 RTA most likely. Type 2 RTA in this case is likely due = wn The 2017 American College of Cardiology/American Heart Asso to multiple myeloma-associated light chain proximal tub- = ciation BP guideline recommends that for adults with a compel- ulopathy. Multiple myeloma is suggested by the presence of oO = wn ling condition (such as aortic dissection, severe preeclampsia or anemia and high gamma globulin fraction (elevated total 35) eclampsia, or pheochromocytoma crisis), systolic BP should be protein and low albumin concentrations). = Qa. reduced to <140 mm Hg during the first hour and to <120 mm Bartter syndrome (Option A) can cause hypokalemia a Hg in aortic dissection. Referral for emergency surgery should and hypophosphatemia but is also associated with metabolic =s =. be considered in all patients with type A aortic dissection given alkalosis and most often presents in childhood. Liddle syn- <2 sa the very high mortality rate associated with this condition. drome (Option B) causes increased sodium reabsorption in oO wn Hydralazine (Option B) can increase myocardial con- the distal nephron with resulting hypertension, metabolic tractility and is not the first-line treatment in this case. alkalosis, and potassium wasting. This patient has a normal Treatment with an IV rapidly acting calcium channel anion gap metabolic acidosis, which excludes Bartter and blocker such as nicardipine (Option C) or with a vasodilator Liddle syndromes. such as nitroprusside (Option D) should not be initiated Type 1 (hypokalemic distal) RTA (Option C) is due to a before B-blockade. In the absence of B—blockade, vasodilator defect in urine acidification in the distal nephron. Because therapy induces reflex activation of the sympathetic nervous of the inability to excrete hydrogen ions, patients develop system, resulting in tachycardia and enhanced ventricular a metabolic acidosis with compensatory hyperchloremia, contraction, which increases aortic wall shear stress. Follow- resulting in a normal anion gap and the inability to acidify ing effective B-blockade, vasodilator therapy can be initiated urine below a pH of 6.0; this patient’s urine pH is 5.0. to reduce the systolic BP to <120 mm Hg. The urine anion gap is positive, reflecting decreased acid excretion in the form of ammonium and chloride. The same defects also cause potassium wasting, and the increased e Intravenous short-acting B,-selective adrenergic proximal resorption of citrate that occurs with metabolic receptor blockers are an initial first-line treatment to acidosis leads to hypocitraturia and increased risk for cal- rapidly lower blood pressure in patients with hyper- cium phosphate kidney stones and nephrocalcinosis. tensive emergency and aortic dissection. Type 4 (hyperkalemic distal) RTA (Option E) due to ¢ In adults with a compelling condition (such as aortic aldosterone deficiency or resistance is associated with a mild dissection, severe preeclampsia or eclampsia, or phe- normal anion gap metabolic acidosis and hyperkalemia, ochromocytoma crisis), systolic blood pressure should which are not seen in this patient.

Item 30 Answer: A Type 2 RTA involves a proximal tubular defect in reclaim- ing bicarbonate and is characterized by a normal anion Educational Objective: Treat a hypertensive emergency gap metabolic acidosis, hypokalemia, glycosuria (without with aortic dissection. hyperglycemia), low-molecular-weight proteinuria, and The most appropriate initial treatment is to administer intrave- renal phosphate wasting (known as Fanconi syndrome when nous (IV) esmolol (Option A). This patient has a hypertensive all features are present). Because distal urine acidification emergency with a type A aortic dissection involving the ascend remains intact, the urine pH is usually <5.5 without alkali ing aorta. For hypertensive emergency with evidence of end- therapy, and the urine anion gap ([Urine Sodium + Urine organ damage, blood pressure (BP) should be rapidly lowered Potassium] - Urine Chloride) would be negative, reflecting using IV short-acting agents. Esmolol is a B,-selective adrenergic increased excretion of acid in the form of ammonium and receptor blocker with a 1- to 2-minute onset of action. Esmolol chloride. This patient’s normal anion gap metabolic acidosis, can rapidly reduce heart rate and BP, thereby reducing aortic low urine pH, hypokalemia, and hypophosphatemia makes PI wall sheer stress and limiting the propagation of the dissection. type 2 RTA most likely. Type 2 RTA in this case is likely due = wn The 2017 American College of Cardiology/American Heart Asso to multiple myeloma-associated light chain proximal tub- = ciation BP guideline recommends that for adults with a compel- ulopathy. Multiple myeloma is suggested by the presence of oO = wn ling condition (such as aortic dissection, severe preeclampsia or anemia and high gamma globulin fraction (elevated total 35) eclampsia, or pheochromocytoma crisis), systolic BP should be protein and low albumin concentrations). = Qa. reduced to <140 mm Hg during the first hour and to <120 mm Bartter syndrome (Option A) can cause hypokalemia a Hg in aortic dissection. Referral for emergency surgery should and hypophosphatemia but is also associated with metabolic =s =. be considered in all patients with type A aortic dissection given alkalosis and most often presents in childhood. Liddle syn- <2 sa the very high mortality rate associated with this condition. drome (Option B) causes increased sodium reabsorption in oO wn Hydralazine (Option B) can increase myocardial con- the distal nephron with resulting hypertension, metabolic tractility and is not the first-line treatment in this case. alkalosis, and potassium wasting. This patient has a normal Treatment with an IV rapidly acting calcium channel anion gap metabolic acidosis, which excludes Bartter and blocker such as nicardipine (Option C) or with a vasodilator Liddle syndromes. such as nitroprusside (Option D) should not be initiated Type 1 (hypokalemic distal) RTA (Option C) is due to a before B-blockade. In the absence of B—blockade, vasodilator defect in urine acidification in the distal nephron. Because therapy induces reflex activation of the sympathetic nervous of the inability to excrete hydrogen ions, patients develop system, resulting in tachycardia and enhanced ventricular a metabolic acidosis with compensatory hyperchloremia, contraction, which increases aortic wall shear stress. Follow- resulting in a normal anion gap and the inability to acidify ing effective B-blockade, vasodilator therapy can be initiated urine below a pH of 6.0; this patient’s urine pH is 5.0. to reduce the systolic BP to <120 mm Hg. The urine anion gap is positive, reflecting decreased acid excretion in the form of ammonium and chloride. The same defects also cause potassium wasting, and the increased e Intravenous short-acting B,-selective adrenergic proximal resorption of citrate that occurs with metabolic receptor blockers are an initial first-line treatment to acidosis leads to hypocitraturia and increased risk for cal- rapidly lower blood pressure in patients with hyper- cium phosphate kidney stones and nephrocalcinosis. tensive emergency and aortic dissection. Type 4 (hyperkalemic distal) RTA (Option E) due to ¢ In adults with a compelling condition (such as aortic aldosterone deficiency or resistance is associated with a mild dissection, severe preeclampsia or eclampsia, or phe- normal anion gap metabolic acidosis and hyperkalemia, ochromocytoma crisis), systolic blood pressure should which are not seen in this patient. be reduced to <140 mm Hg during the first hour and to <120 mm Hg in aortic dissection. © Type 2 (proximal) renal tubular acidosis is character- ized by a normal anion gap metabolic acidosis, Bibliography hypokalemia, glycosuria (without hyperglycemia), Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, low-molecular-weight proteinuria, and renal phos- detection, evaluation, and management of high blood pressure in adults: phate wasting. a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. ¢ Type 1 (hypokalemic distal) renal tubular acidosis is 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016/j.jacc.2017.11.006. characterized by a normal anion gap metabolic acidosis, hypokalemia, urine pH >6.0, and calcium phosphate Item 31 Answer: D kidney stones.

be reduced to <140 mm Hg during the first hour and to <120 mm Hg in aortic dissection. © Type 2 (proximal) renal tubular acidosis is character- ized by a normal anion gap metabolic acidosis, Bibliography hypokalemia, glycosuria (without hyperglycemia), Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, low-molecular-weight proteinuria, and renal phos- detection, evaluation, and management of high blood pressure in adults: phate wasting. a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. ¢ Type 1 (hypokalemic distal) renal tubular acidosis is 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016/j.jacc.2017.11.006. characterized by a normal anion gap metabolic acidosis, hypokalemia, urine pH >6.0, and calcium phosphate Item 31 Answer: D kidney stones. Educational Objective: Diagnose type 2 (proximal) renal tubular acidosis. Bibliography Rastegar M, Nagami GT. Non-anion gap metabolic acidosis: a clinical The most likely cause of this patient’s laboratory findings is approach to evaluation. Am J Kidney Dis. 2017;69:296-301. [PMID: type 2 (proximal) renal tubular acidosis (RTA) (Option D). 28029394] doi:10.1053 /j-ajkd.2016.09.013 136

Item 32 Answer: B hematuria should prompt urology referral even if self- limited. Hematuria is most often of nonglomerular origin. Ifa Educational Objective: Treat stage 2 hypertension with nephrologic cause of hematuria is not suggested, it may indi- combination drug therapy. cate a malignancy. Guidelines from the American Urological The most appropriate additional therapy is amlodipine- Association recommend that patients 240 years of age or of valsartan (Option B). This patient has stage 2 hypertension any age with risk factors for lower urinary tract malignancy (systolic blood pressure >140 mm Hg or diastolic blood pres- (such as irritative voiding symptoms, smoking history, aniline sure >90 mm Hg). For patients with stage 2 hypertension dye exposure, or cyclophosphamide exposure) undergo eval- with or without cardiovascular risk or disease, pharmacologic uation for malignancy with imaging. If imaging is negative, management in addition to therapeutic lifestyle interventions cystoscopy should be performed. This patient is a 43-year-old is recommended. The 2017 American College of Cardiology/ man without evidence of glomerular disease (no proteinuria American Heart Association blood pressure (BP) guideline or increased serum creatinine level) or infection (no leukocy- recommends combination therapy with two first-line anti- turia, negative nitrites, and no leukocyte esterase) and nega- nn fy hypertensive drugs of different classes for adults with stage 2 tive imaging of the upper genitourinary tract. Therefore, it is s

Item 32 Answer: B hematuria should prompt urology referral even if self- limited. Hematuria is most often of nonglomerular origin. Ifa Educational Objective: Treat stage 2 hypertension with nephrologic cause of hematuria is not suggested, it may indi- combination drug therapy. cate a malignancy. Guidelines from the American Urological The most appropriate additional therapy is amlodipine- Association recommend that patients 240 years of age or of valsartan (Option B). This patient has stage 2 hypertension any age with risk factors for lower urinary tract malignancy (systolic blood pressure >140 mm Hg or diastolic blood pres- (such as irritative voiding symptoms, smoking history, aniline sure >90 mm Hg). For patients with stage 2 hypertension dye exposure, or cyclophosphamide exposure) undergo eval- with or without cardiovascular risk or disease, pharmacologic uation for malignancy with imaging. If imaging is negative, management in addition to therapeutic lifestyle interventions cystoscopy should be performed. This patient is a 43-year-old is recommended. The 2017 American College of Cardiology/ man without evidence of glomerular disease (no proteinuria American Heart Association blood pressure (BP) guideline or increased serum creatinine level) or infection (no leukocy- recommends combination therapy with two first-line anti- turia, negative nitrites, and no leukocyte esterase) and nega- nn fy hypertensive drugs of different classes for adults with stage 2 tive imaging of the upper genitourinary tract. Therefore, it is s hypertension and an average BP that is 20/10 mm Hg above appropriate to assess for bladder pathology using cystoscopy. = their BP target. Based on the presence of hypertension, dys- Kidney biopsy (Option B) in a patient with hematuria +o oC lipidemia, and cigarette smoking, this patient has a calculated is not indicated in the absence of evidence of glomerular sc Se 10-year atherosclerotic cardiovascular disease (ASCVD) event disease. A glomerular origin is suggested by concurrent pro- cs

hypertension and an average BP that is 20/10 mm Hg above appropriate to assess for bladder pathology using cystoscopy. = their BP target. Based on the presence of hypertension, dys- Kidney biopsy (Option B) in a patient with hematuria +o oC lipidemia, and cigarette smoking, this patient has a calculated is not indicated in the absence of evidence of glomerular sc Se 10-year atherosclerotic cardiovascular disease (ASCVD) event disease. A glomerular origin is suggested by concurrent pro- cs risk of 10%. The target BP for patients with established car- teinuria, presence of dysmorphic erythrocytes, increased wn ex o diovascular disease or for patients with an estimated ASCVD serum creatinine, or decrease in estimated glomerular filtra- = event risk >10% is 130/80 mm Hg. This patient has an elevated tion rate. This patient has no indication for a kidney biopsy. wn 4 10-year ASCVD event risk and his BP is >20/10 mm Hg above Repeat urinalysis (Option C) is not indicated. This patient’s 4

risk of 10%. The target BP for patients with established car- teinuria, presence of dysmorphic erythrocytes, increased wn ex o diovascular disease or for patients with an estimated ASCVD serum creatinine, or decrease in estimated glomerular filtra- = event risk >10% is 130/80 mm Hg. This patient has an elevated tion rate. This patient has no indication for a kidney biopsy. wn 4 10-year ASCVD event risk and his BP is >20/10 mm Hg above Repeat urinalysis (Option C) is not indicated. This patient’s 4 target; therefore, combination drug therapy is indicated. To macroscopic hematuria should prompt urologic investigation maximize adherence, using a fixed-dose combination agent now. A single incident of hematuria warrants further investiga- may be more effective than adding two separate antihyper- tion, even if the patient has a bleeding disorder or is receiving tensive agents. antiplatelet or anticoagulation therapy. If menstruation, viral Starting chlorthalidone, amlodipine, or valsartan illness, urinary tract infection, vigorous exercise, or another (Options A, C, D) as single-agent therapy would each be benign cause is suspected, urinalysis should be repeated after appropriate as first-line therapy for patients with stage 1 the cause is resolved. Otherwise, as in this case, further evalu- hypertension (systolic BP of 130-139 mm Hg or diastolic BP ation should ensue without additional urinalysis. of 80-89 mm Hg). Combination therapy is recommended for The absence of proteinuria makes a glomerular cause patients with stage 2 hypertension and an average BP that is of hematuria less likely. Although a 24-hour urine protein 20/10 mm Hg above their BP target. collection (Option D) is the gold standard for determin- ing proteinuria, random urine albumin-creatinine ratio and protein-creatinine ratio correlate well with timed collec- e A blood pressure <130/80 mm Hg is recommended for tions. This patient has a normal urine protein-creatinine adults with hypertension and cardiovascular disease ratio; therefore, a 24-hour collection is not indicated. or a 10-year atherosclerotic cardiovascular disease event risk 210%. e Patients with gross hematuria who are >35 years of ¢ Combination therapy with two first-line antihyperten- sive medications of different classes is recommended age or have risk factors for lower urinary tract malig-

target; therefore, combination drug therapy is indicated. To macroscopic hematuria should prompt urologic investigation maximize adherence, using a fixed-dose combination agent now. A single incident of hematuria warrants further investiga- may be more effective than adding two separate antihyper- tion, even if the patient has a bleeding disorder or is receiving tensive agents. antiplatelet or anticoagulation therapy. If menstruation, viral Starting chlorthalidone, amlodipine, or valsartan illness, urinary tract infection, vigorous exercise, or another (Options A, C, D) as single-agent therapy would each be benign cause is suspected, urinalysis should be repeated after appropriate as first-line therapy for patients with stage 1 the cause is resolved. Otherwise, as in this case, further evalu- hypertension (systolic BP of 130-139 mm Hg or diastolic BP ation should ensue without additional urinalysis. of 80-89 mm Hg). Combination therapy is recommended for The absence of proteinuria makes a glomerular cause patients with stage 2 hypertension and an average BP that is of hematuria less likely. Although a 24-hour urine protein 20/10 mm Hg above their BP target. collection (Option D) is the gold standard for determin- ing proteinuria, random urine albumin-creatinine ratio and protein-creatinine ratio correlate well with timed collec- e A blood pressure <130/80 mm Hg is recommended for tions. This patient has a normal urine protein-creatinine adults with hypertension and cardiovascular disease ratio; therefore, a 24-hour collection is not indicated. or a 10-year atherosclerotic cardiovascular disease event risk 210%. e Patients with gross hematuria who are >35 years of ¢ Combination therapy with two first-line antihyperten- sive medications of different classes is recommended age or have risk factors for lower urinary tract malig- for adults with stage 2 hypertension and an average nancy should be evaluated for malignancy.

target; therefore, combination drug therapy is indicated. To macroscopic hematuria should prompt urologic investigation maximize adherence, using a fixed-dose combination agent now. A single incident of hematuria warrants further investiga- may be more effective than adding two separate antihyper- tion, even if the patient has a bleeding disorder or is receiving tensive agents. antiplatelet or anticoagulation therapy. If menstruation, viral Starting chlorthalidone, amlodipine, or valsartan illness, urinary tract infection, vigorous exercise, or another (Options A, C, D) as single-agent therapy would each be benign cause is suspected, urinalysis should be repeated after appropriate as first-line therapy for patients with stage 1 the cause is resolved. Otherwise, as in this case, further evalu- hypertension (systolic BP of 130-139 mm Hg or diastolic BP ation should ensue without additional urinalysis. of 80-89 mm Hg). Combination therapy is recommended for The absence of proteinuria makes a glomerular cause patients with stage 2 hypertension and an average BP that is of hematuria less likely. Although a 24-hour urine protein 20/10 mm Hg above their BP target. collection (Option D) is the gold standard for determin- ing proteinuria, random urine albumin-creatinine ratio and protein-creatinine ratio correlate well with timed collec- e A blood pressure <130/80 mm Hg is recommended for tions. This patient has a normal urine protein-creatinine adults with hypertension and cardiovascular disease ratio; therefore, a 24-hour collection is not indicated. or a 10-year atherosclerotic cardiovascular disease event risk 210%. e Patients with gross hematuria who are >35 years of ¢ Combination therapy with two first-line antihyperten- sive medications of different classes is recommended age or have risk factors for lower urinary tract malig- for adults with stage 2 hypertension and an average nancy should be evaluated for malignancy. blood pressure (BP) of >20/10 mm Hg above BP target. e Evaluation of gross hematuria includes imaging of the lower urinary tract followed by cystoscopy if imaging Bibliography is negative. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Bibliography a report of the American College of Cardiology/American Heart Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Guideline. J Urol. 2020;204:778-786. [PMID: 32698717] doi:10.1097/ 2018;71:e127-e248. [PMID: 29146535] JU.0000000000001297

blood pressure (BP) of >20/10 mm Hg above BP target. e Evaluation of gross hematuria includes imaging of the lower urinary tract followed by cystoscopy if imaging Bibliography is negative. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Bibliography a report of the American College of Cardiology/American Heart Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Guideline. J Urol. 2020;204:778-786. [PMID: 32698717] doi:10.1097/ 2018;71:e127-e248. [PMID: 29146535] JU.0000000000001297 Item 33 Answer: A Item 34 Answer: D Educational Objective: Evaluate gross hematuria. Educational Objective: Manage hepatitis C virus infec- tion in a patient with end-stage kidney disease. Cystoscopy (Option A) is the most appropriate diagnostic test to perform next in this patient. Hematuria is frequently The most appropriate management is to discuss hepatitis C encountered among adults in ambulatory care. Macroscopic virus (HCV) treatment and timing (Option D). This patient 137

See ate Ses has evidence of HCV infection and hepatitis B virus (HBV) chlorpheniramine, a drug with anticholinergic properties. immunity (negative hepatitis B surface antigen, positive Postrenal acute kidney injury (AKI) results from urinary tract hepatitis B surface antibody). Screening patients for both obstruction. If left uncorrected, the elevated tubular pressure viruses on admission to a dialysis center is part of ongo- can cause chronic and end-stage kidney disease. Postre- ing infection control surveillance within a dialysis center. nal obstruction due to bladder outlet obstruction should Identification of infection is important because treatment be suspected in patients with a history of BPH and diabetes can be offered. All patients with HCV infection should be mellitus (neurogenic bladder). Symptoms of bladder outlet considered for treatment unless there are significant life- obstruction may include abdominal fullness or pain; urinary limiting comorbidities. Treatment regimens for HCV infec- frequency, urgency, and hesitancy; nocturia; and incomplete tion include a combination of direct-acting antivirals, using voiding. The diagnosis is supported by a distended bladder different mechanisms to prevent viral reproduction. Reg- and prostate enlargement on physical examination. In post- imens are chosen based on genotype, previous treatment renal obstruction, urine sediment is often unremarkable, PH experience and response, and fibrosis status. The timing but microscopic hematuria may be present. Bladder outlet = nn of HCV treatment must be individualized in patients such obstruction is confirmed by an elevated postvoid residual = as this one with end-stage kidney disease (ESKD) who are bladder volume by ultrasonography. If the obstruction is oO = wn potential kidney transplant recipients. It is important to relieved within 1 to 2 weeks, recovery of kidney function is y J discuss treatment and treatment timing with this patient excellent. a. and the kidney transplant program. In patients with ESKD, Obstruction of the upper tract (ureters or renal pelvis) oO =e treatment for concurrent HCV infection can be timed before must be bilateral to cause AKI (unless obstruction occurs ina a. kidney transplantation or after transplantation if receiving single kidney); causes may include nephrolithiasis, abdom- 2 = an HCV-infected donor kidney. inal or pelvic surgeries or radiation, pelvic malignancies, or @o 7.) Antiviral treatment is safe and generally well tolerated retroperitoneal fibrosis or lymphadenopathy. Kidney ultra- in patients with ESKD, and the presence of HCV infection is sonography (Option B) is the initial modality of choice for not a contraindication for kidney transplantation. Neither diagnosing upper tract obstruction. Although kidney ultra- avoiding antiviral therapy nor transplantation is appropriate sonography may ultimately be performed, the next manage- for this patient (Option A). ment step is bladder ultrasonography and possible bladder First-line treatment for HBV infection is entecavir catheterization because bladder outlet obstruction is more (Option B) or tenofovir. However, this patient is immune to likely to occur in a man with BPH recently exposed to a hepatitis B, and treatment is not warranted. medication with anticholinergic effects. Pegylated interferon and ribavirin (Option C) would not IgG4-related autoimmune pancreatitis can be associ- be indicated for this patient before a discussion about the ated with other IgG4-related diseases, including retroper timing of HCV therapy. In addition, many direct-acting anti- itoneal fibrosis and obstructive uropathy. CT with contrast viral regimens are available and are safe for use in patients or MRI of the abdomen and pelvis (Option C) are the initial with chronic kidney disease or ESKD with significantly less imaging studies. However, in this patient with BPH, the ini morbidity compared with interferon therapy. tial diagnostic modality is bladder ultrasonography. Failure to establish a diagnosis should prompt appropriate imaging tests. e In patients with end-stage kidney disease, treatment Patients with acute ureteral obstruction caused by for concurrent hepatitis C virus infection can be nephrolithiasis may present with ureteral colic. In this sce- timed before kidney transplantation or after trans- nario, a noncontrast CT of the abdomen and pelvis (Option plantation if receiving a hepatitis C-infected donor D) may provide the correct diagnosis. However, there are no kidney. symptoms to support this diagnosis, and bladder ultraso- nography will establish the most likely diagnosis. Bibliography Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 clinical practice guideline for the prevention, diag- e Postrenal acute kidney injury results from urinary tract nosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl (2011). 2018;8:91-165. [PMID: 30675443] doi:10.1016/j. obstruction that is readily reversible if recognized early kisu.2018.06.001 and corrected promptly.

has evidence of HCV infection and hepatitis B virus (HBV) chlorpheniramine, a drug with anticholinergic properties. immunity (negative hepatitis B surface antigen, positive Postrenal acute kidney injury (AKI) results from urinary tract hepatitis B surface antibody). Screening patients for both obstruction. If left uncorrected, the elevated tubular pressure viruses on admission to a dialysis center is part of ongo- can cause chronic and end-stage kidney disease. Postre- ing infection control surveillance within a dialysis center. nal obstruction due to bladder outlet obstruction should Identification of infection is important because treatment be suspected in patients with a history of BPH and diabetes can be offered. All patients with HCV infection should be mellitus (neurogenic bladder). Symptoms of bladder outlet considered for treatment unless there are significant life- obstruction may include abdominal fullness or pain; urinary limiting comorbidities. Treatment regimens for HCV infec- frequency, urgency, and hesitancy; nocturia; and incomplete tion include a combination of direct-acting antivirals, using voiding. The diagnosis is supported by a distended bladder different mechanisms to prevent viral reproduction. Reg- and prostate enlargement on physical examination. In post- imens are chosen based on genotype, previous treatment renal obstruction, urine sediment is often unremarkable, PH experience and response, and fibrosis status. The timing but microscopic hematuria may be present. Bladder outlet = nn of HCV treatment must be individualized in patients such obstruction is confirmed by an elevated postvoid residual = as this one with end-stage kidney disease (ESKD) who are bladder volume by ultrasonography. If the obstruction is oO = wn potential kidney transplant recipients. It is important to relieved within 1 to 2 weeks, recovery of kidney function is y J discuss treatment and treatment timing with this patient excellent. a. and the kidney transplant program. In patients with ESKD, Obstruction of the upper tract (ureters or renal pelvis) oO =e treatment for concurrent HCV infection can be timed before must be bilateral to cause AKI (unless obstruction occurs ina a. kidney transplantation or after transplantation if receiving single kidney); causes may include nephrolithiasis, abdom- 2 = an HCV-infected donor kidney. inal or pelvic surgeries or radiation, pelvic malignancies, or @o 7.) Antiviral treatment is safe and generally well tolerated retroperitoneal fibrosis or lymphadenopathy. Kidney ultra- in patients with ESKD, and the presence of HCV infection is sonography (Option B) is the initial modality of choice for not a contraindication for kidney transplantation. Neither diagnosing upper tract obstruction. Although kidney ultra- avoiding antiviral therapy nor transplantation is appropriate sonography may ultimately be performed, the next manage- for this patient (Option A). ment step is bladder ultrasonography and possible bladder First-line treatment for HBV infection is entecavir catheterization because bladder outlet obstruction is more (Option B) or tenofovir. However, this patient is immune to likely to occur in a man with BPH recently exposed to a hepatitis B, and treatment is not warranted. medication with anticholinergic effects. Pegylated interferon and ribavirin (Option C) would not IgG4-related autoimmune pancreatitis can be associ- be indicated for this patient before a discussion about the ated with other IgG4-related diseases, including retroper timing of HCV therapy. In addition, many direct-acting anti- itoneal fibrosis and obstructive uropathy. CT with contrast viral regimens are available and are safe for use in patients or MRI of the abdomen and pelvis (Option C) are the initial with chronic kidney disease or ESKD with significantly less imaging studies. However, in this patient with BPH, the ini morbidity compared with interferon therapy. tial diagnostic modality is bladder ultrasonography. Failure to establish a diagnosis should prompt appropriate imaging tests. e In patients with end-stage kidney disease, treatment Patients with acute ureteral obstruction caused by for concurrent hepatitis C virus infection can be nephrolithiasis may present with ureteral colic. In this sce- timed before kidney transplantation or after trans- nario, a noncontrast CT of the abdomen and pelvis (Option plantation if receiving a hepatitis C-infected donor D) may provide the correct diagnosis. However, there are no kidney. symptoms to support this diagnosis, and bladder ultraso- nography will establish the most likely diagnosis. Bibliography Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 clinical practice guideline for the prevention, diag- e Postrenal acute kidney injury results from urinary tract nosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl (2011). 2018;8:91-165. [PMID: 30675443] doi:10.1016/j. obstruction that is readily reversible if recognized early kisu.2018.06.001 and corrected promptly. e Postrenal obstruction should be suspected in patients

has evidence of HCV infection and hepatitis B virus (HBV) chlorpheniramine, a drug with anticholinergic properties. immunity (negative hepatitis B surface antigen, positive Postrenal acute kidney injury (AKI) results from urinary tract hepatitis B surface antibody). Screening patients for both obstruction. If left uncorrected, the elevated tubular pressure viruses on admission to a dialysis center is part of ongo- can cause chronic and end-stage kidney disease. Postre- ing infection control surveillance within a dialysis center. nal obstruction due to bladder outlet obstruction should Identification of infection is important because treatment be suspected in patients with a history of BPH and diabetes can be offered. All patients with HCV infection should be mellitus (neurogenic bladder). Symptoms of bladder outlet considered for treatment unless there are significant life- obstruction may include abdominal fullness or pain; urinary limiting comorbidities. Treatment regimens for HCV infec- frequency, urgency, and hesitancy; nocturia; and incomplete tion include a combination of direct-acting antivirals, using voiding. The diagnosis is supported by a distended bladder different mechanisms to prevent viral reproduction. Reg- and prostate enlargement on physical examination. In post- imens are chosen based on genotype, previous treatment renal obstruction, urine sediment is often unremarkable, PH experience and response, and fibrosis status. The timing but microscopic hematuria may be present. Bladder outlet = nn of HCV treatment must be individualized in patients such obstruction is confirmed by an elevated postvoid residual = as this one with end-stage kidney disease (ESKD) who are bladder volume by ultrasonography. If the obstruction is oO = wn potential kidney transplant recipients. It is important to relieved within 1 to 2 weeks, recovery of kidney function is y J discuss treatment and treatment timing with this patient excellent. a. and the kidney transplant program. In patients with ESKD, Obstruction of the upper tract (ureters or renal pelvis) oO =e treatment for concurrent HCV infection can be timed before must be bilateral to cause AKI (unless obstruction occurs ina a. kidney transplantation or after transplantation if receiving single kidney); causes may include nephrolithiasis, abdom- 2 = an HCV-infected donor kidney. inal or pelvic surgeries or radiation, pelvic malignancies, or @o 7.) Antiviral treatment is safe and generally well tolerated retroperitoneal fibrosis or lymphadenopathy. Kidney ultra- in patients with ESKD, and the presence of HCV infection is sonography (Option B) is the initial modality of choice for not a contraindication for kidney transplantation. Neither diagnosing upper tract obstruction. Although kidney ultra- avoiding antiviral therapy nor transplantation is appropriate sonography may ultimately be performed, the next manage- for this patient (Option A). ment step is bladder ultrasonography and possible bladder First-line treatment for HBV infection is entecavir catheterization because bladder outlet obstruction is more (Option B) or tenofovir. However, this patient is immune to likely to occur in a man with BPH recently exposed to a hepatitis B, and treatment is not warranted. medication with anticholinergic effects. Pegylated interferon and ribavirin (Option C) would not IgG4-related autoimmune pancreatitis can be associ- be indicated for this patient before a discussion about the ated with other IgG4-related diseases, including retroper timing of HCV therapy. In addition, many direct-acting anti- itoneal fibrosis and obstructive uropathy. CT with contrast viral regimens are available and are safe for use in patients or MRI of the abdomen and pelvis (Option C) are the initial with chronic kidney disease or ESKD with significantly less imaging studies. However, in this patient with BPH, the ini morbidity compared with interferon therapy. tial diagnostic modality is bladder ultrasonography. Failure to establish a diagnosis should prompt appropriate imaging tests. e In patients with end-stage kidney disease, treatment Patients with acute ureteral obstruction caused by for concurrent hepatitis C virus infection can be nephrolithiasis may present with ureteral colic. In this sce- timed before kidney transplantation or after trans- nario, a noncontrast CT of the abdomen and pelvis (Option plantation if receiving a hepatitis C-infected donor D) may provide the correct diagnosis. However, there are no kidney. symptoms to support this diagnosis, and bladder ultraso- nography will establish the most likely diagnosis. Bibliography Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 clinical practice guideline for the prevention, diag- e Postrenal acute kidney injury results from urinary tract nosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl (2011). 2018;8:91-165. [PMID: 30675443] doi:10.1016/j. obstruction that is readily reversible if recognized early kisu.2018.06.001 and corrected promptly. e Postrenal obstruction should be suspected in patients Item 35 Answer: A with a history of benign prostatic hyperplasia, diabetes mellitus, nephrolithiasis, abdominal or pelvic surgeries Educational Objective: Diagnose postrenal obstructive uropathy. or radiation, pelvic malignancies, or retroperitoneal fibrosis or lymphadenopathy. The most appropriate initial step in management is blad- der ultrasonography (Option A). This patient most likely Bibliography has postrenal obstructive uropathy secondary to benign Levey AS, James MT. Acute kidney injury. Ann Intern Med. 2017;167:ITC66- prostatic hyperplasia (BPH) and the recent introduction of ITC80. [PMID: 29114754] doi:10.7326/AITC201711070

Item 35 Answer: A with a history of benign prostatic hyperplasia, diabetes mellitus, nephrolithiasis, abdominal or pelvic surgeries Educational Objective: Diagnose postrenal obstructive uropathy. or radiation, pelvic malignancies, or retroperitoneal fibrosis or lymphadenopathy. The most appropriate initial step in management is blad- der ultrasonography (Option A). This patient most likely Bibliography has postrenal obstructive uropathy secondary to benign Levey AS, James MT. Acute kidney injury. Ann Intern Med. 2017;167:ITC66- prostatic hyperplasia (BPH) and the recent introduction of ITC80. [PMID: 29114754] doi:10.7326/AITC201711070 138

Answers and Critiques Item 36 Answer: A Item 37 Answer: D Educational Objective: Diagnose focal segmental Educational Objective: Treat hypertension in a patient glomerulosclerosis. with diabetes mellitus and albuminuria using an ACE inhibitor or angiotensin receptor blocker. The most likely diagnosis is focal segmental glomerulosclerosis (FSGS) (Option A). In the United States, FSGS currently accounts The most appropriate treatment is to begin losartan (Option D). for up to 40% of primary nephrotic syndromes in adults. FSGS Blood pressure (BP) control is more difficult to achieve in is the most common form of the nephrotic syndrome in Black patients with diabetes mellitus, necessitating use of combi- patients. Individuals of African ancestry carry approximately a nation therapy in most of these patients. The 2017 American five times higher risk for FSGS than those of European descent, College of Cardiology/American Heart Association guideline likely mediated in large part by variants in the APOL1 gene, which recommends a target BP of <130/80 mm Hg for patients with is likely responsible for this patient’s FSGS as well as the kidney hypertension and diabetes. The American Diabetes Associ- disease found in other members of his family. Black persons ation (ADA) recommends that most patients with diabetes wn a develop kidney failure at rates four to five times higher than White and hypertension should be treated to a target BP of 140/90 = persons, and the APOL1 gene is attributed to a large fraction of mm Hg; 130/80 mm Hg may be appropriate for individuals = this health disparity. Two risk alleles for kidney disease (G1 and at higher risk (existing atherosclerotic cardiovascular disease ‘= rs) G2) have been identified in the APOL1 gene. The transmission of [ASCVD] or 10-year ASCVD risk 215%), if it can be achieved <s disease risk is consistent with recessive inheritance. Approx- safely. In adults with diabetes and hypertension, all first- = Ls] imately 12% to 15% of African Americans inherit a high-risk line classes of antihypertensive agents (i.e., diuretics, ACE wn i

Item 36 Answer: A Item 37 Answer: D Educational Objective: Diagnose focal segmental Educational Objective: Treat hypertension in a patient glomerulosclerosis. with diabetes mellitus and albuminuria using an ACE inhibitor or angiotensin receptor blocker. The most likely diagnosis is focal segmental glomerulosclerosis (FSGS) (Option A). In the United States, FSGS currently accounts The most appropriate treatment is to begin losartan (Option D). for up to 40% of primary nephrotic syndromes in adults. FSGS Blood pressure (BP) control is more difficult to achieve in is the most common form of the nephrotic syndrome in Black patients with diabetes mellitus, necessitating use of combi- patients. Individuals of African ancestry carry approximately a nation therapy in most of these patients. The 2017 American five times higher risk for FSGS than those of European descent, College of Cardiology/American Heart Association guideline likely mediated in large part by variants in the APOL1 gene, which recommends a target BP of <130/80 mm Hg for patients with is likely responsible for this patient’s FSGS as well as the kidney hypertension and diabetes. The American Diabetes Associ- disease found in other members of his family. Black persons ation (ADA) recommends that most patients with diabetes wn a develop kidney failure at rates four to five times higher than White and hypertension should be treated to a target BP of 140/90 = persons, and the APOL1 gene is attributed to a large fraction of mm Hg; 130/80 mm Hg may be appropriate for individuals = this health disparity. Two risk alleles for kidney disease (G1 and at higher risk (existing atherosclerotic cardiovascular disease ‘= rs) G2) have been identified in the APOL1 gene. The transmission of [ASCVD] or 10-year ASCVD risk 215%), if it can be achieved <s disease risk is consistent with recessive inheritance. Approx- safely. In adults with diabetes and hypertension, all first- = Ls] imately 12% to 15% of African Americans inherit a high-risk line classes of antihypertensive agents (i.e., diuretics, ACE wn i APOLI genotype; this accounts for a large fraction of nondiabetic inhibitors, angiotensin receptor blockers [ARBs], and calcium 7 = kidney disease in African Americans that in the past has been channel blockers) are useful and effective. ACE inhibitors or nn = attributed to hypertension but would appear as FSGS on biopsy. ARBs are the preferred drug classes for treatment of hyper- <x Persons with a high-risk APOL1 genotype have an approximately tension for patients with diabetes and albuminuria (albumin- 10-fold increased risk for FSGS and a 7-fold increased risk for creatinine ratio [300 mg/g) and in adults with hypertension hypertension-attributed end-stage kidney disease. and chronic kidney disease (stage G3 or higher or stage G1 Kidney involvement in systemic lupus erythematosus or G2 with albuminuria) to slow kidney disease progression. (SLE) is common, and lupus nephritis (LN) (Option B) is a major Among the drug classes, ACE inhibitors and ARBs have the source of morbidity. Patients typically present with extrarenal best efficacy on urinary albumin excretion and demonstrate symptoms of SLE at the time of diagnosis of LN, with active a significant reduction in disease progression. The ADA also lupus serologies and low complement levels. Occasionally, LN recommends use of an ACE inhibitor or ARB at the maximum may be the initial manifestation. Patients with class I or II LN tolerated dose indicated as first-line treatment for hyperten- may have minimal or no kidney findings, and those with class sion in patients with diabetes and albuminuria. Ill or IV present with varying degrees of the nephritic syndrome. Although first-line therapy in patients with diabetes Patients with class V LN typically present with proteinuria. can include a thiazide diuretic or a calcium channel blocker Membranous nephropathy (MN) (Option C) is the most (e.g., amlodipine) (Option A), the presence of albuminuria is common cause of idiopathic nephrotic syndrome in adult White an indication for the addition of a renin-angiotensin system persons. MN may also be associated with infections (hepatitis B inhibitor such as losartan. and C, malaria, syphilis), SLE, medications (gold salts, NSAIDs), Due to the absence of outcome data, B-blockers such as and malignancies (solid tumors, lymphomas). In most patients atenolol (Option B) are not usually recommended as initial with idiopathic MN, circulating antibodies directed to podocyte antihypertensive medication therapy. However, they can be surface antigens (phospholipase A2 receptor) activate comple- used in special populations, such as patients with a previous ment and damage the glomerular basement membrane. myocardial infarction or heart failure, in which outcome Minimal change glomerulopathy (MCG) (Option D) is data exist. the most common cause of idiopathic nephrotic syndrome Doxazosin (Option C) is not a typical second drug added in children and accounts for approximately 10% of cases to thiazide diuretic therapy because of its side-effect pro- in adults. Secondary causes of MCG include medications file, which includes orthostatic hypotension. In addition, (NSAIDs, lithium, pamidronate, the interferons) and malig- doxazosin is not as efficacious as ACE inhibitors or ARBs in nancies (Hodgkin lymphoma and thymoma). preventing the progression of kidney disease.

APOLI genotype; this accounts for a large fraction of nondiabetic inhibitors, angiotensin receptor blockers [ARBs], and calcium 7 = kidney disease in African Americans that in the past has been channel blockers) are useful and effective. ACE inhibitors or nn = attributed to hypertension but would appear as FSGS on biopsy. ARBs are the preferred drug classes for treatment of hyper- <x Persons with a high-risk APOL1 genotype have an approximately tension for patients with diabetes and albuminuria (albumin- 10-fold increased risk for FSGS and a 7-fold increased risk for creatinine ratio [300 mg/g) and in adults with hypertension hypertension-attributed end-stage kidney disease. and chronic kidney disease (stage G3 or higher or stage G1 Kidney involvement in systemic lupus erythematosus or G2 with albuminuria) to slow kidney disease progression. (SLE) is common, and lupus nephritis (LN) (Option B) is a major Among the drug classes, ACE inhibitors and ARBs have the source of morbidity. Patients typically present with extrarenal best efficacy on urinary albumin excretion and demonstrate symptoms of SLE at the time of diagnosis of LN, with active a significant reduction in disease progression. The ADA also lupus serologies and low complement levels. Occasionally, LN recommends use of an ACE inhibitor or ARB at the maximum may be the initial manifestation. Patients with class I or II LN tolerated dose indicated as first-line treatment for hyperten- may have minimal or no kidney findings, and those with class sion in patients with diabetes and albuminuria. Ill or IV present with varying degrees of the nephritic syndrome. Although first-line therapy in patients with diabetes Patients with class V LN typically present with proteinuria. can include a thiazide diuretic or a calcium channel blocker Membranous nephropathy (MN) (Option C) is the most (e.g., amlodipine) (Option A), the presence of albuminuria is common cause of idiopathic nephrotic syndrome in adult White an indication for the addition of a renin-angiotensin system persons. MN may also be associated with infections (hepatitis B inhibitor such as losartan. and C, malaria, syphilis), SLE, medications (gold salts, NSAIDs), Due to the absence of outcome data, B-blockers such as and malignancies (solid tumors, lymphomas). In most patients atenolol (Option B) are not usually recommended as initial with idiopathic MN, circulating antibodies directed to podocyte antihypertensive medication therapy. However, they can be surface antigens (phospholipase A2 receptor) activate comple- used in special populations, such as patients with a previous ment and damage the glomerular basement membrane. myocardial infarction or heart failure, in which outcome Minimal change glomerulopathy (MCG) (Option D) is data exist. the most common cause of idiopathic nephrotic syndrome Doxazosin (Option C) is not a typical second drug added in children and accounts for approximately 10% of cases to thiazide diuretic therapy because of its side-effect pro- in adults. Secondary causes of MCG include medications file, which includes orthostatic hypotension. In addition, (NSAIDs, lithium, pamidronate, the interferons) and malig- doxazosin is not as efficacious as ACE inhibitors or ARBs in nancies (Hodgkin lymphoma and thymoma). preventing the progression of kidney disease. ¢ Focal segmental glomerulosclerosis is the most common e In adults with diabetes mellitus and hypertension, diu- form of the nephrotic syndrome in Black patients, likely retics, ACE inhibitors, angiotensin receptor blockers, mediated in large part by variants in the APOL1 gene. and calcium channel blockers are all effective agents.

¢ Focal segmental glomerulosclerosis is the most common e In adults with diabetes mellitus and hypertension, diu- form of the nephrotic syndrome in Black patients, likely retics, ACE inhibitors, angiotensin receptor blockers, mediated in large part by variants in the APOL1 gene. and calcium channel blockers are all effective agents. Bibliography e ACE inhibitors or angiotensin receptor blockers are the Freedman BI, Limou S, Ma L, et al. APOLI-associated nephropathy: A key preferred drug classes for treatment of hypertension in contributor to racial disparities in CKD. Am J Kidney Dis. 2018;72:S8-S16. patients with diabetes mellitus and albuminuria. [PMID: 30343724] doi:10.1053/j.ajkd.2018.06.020 139

ee re ee Bibliography Item 39 Answer: D Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. Educational Objective: Treat hypertension in a patient [PMID: 31060074] doi:10.7326/AITC201905070 with type 2 diabetes mellitus and albuminuria.

Bibliography Item 39 Answer: D Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. Educational Objective: Treat hypertension in a patient [PMID: 31060074] doi:10.7326/AITC201905070 with type 2 diabetes mellitus and albuminuria. The most appropriate initial therapy is lisinopril (Option D), an Item 38 Answer: B ACE inhibitor, to treat hypertension in this patient with type Educational Objective: Diagnose urinary tract infection 2 diabetes mellitus and albuminuria. Although this patient’s caused by a urea-splitting organism. serum creatinine level is normal, she has evidence of chronic kidney disease (CKD) based on the presence of albuminuria Proteus mirabilis (Option B) is the most likely organism (urine albumin-creatinine ratio >30 mg/g). Albuminuria and responsible for this patient’s infection. This patient most likely uncontrolled blood pressure increase her risk for progression has a urinary tract infection (UTI) caused by Proteus, or other of CKD. Several large randomized controlled trials showed urea-splitting organisms such as Klebsiella or, less frequently, = that use of an ACE inhibitor or angiotensin receptor blocker Pseudomonas. These bacteria secrete urease, which enzymat- = (ARB) can result in decreased progression of albuminuria na ically hydrolyzes urea into carbon dioxide and ammonium, = and CKD, which may include doubling of serum creatinine @ which markedly increases urine pH and results in the pre- od or progression to end-stage kidney disease, in patients with wn cipitation of magnesium ammonium phosphate, also known So diabetes and albuminuria. = as struvite. On urinalysis, the urine pH will be >7.5. Struvite Qa. Although first-line antihypertensive therapy in non- crystals are recognized by their coffin-lid appearance. Struvite a Black patients in the absence of proteinuria includes a thia- oe crystals can rapidly form large stones in the renal pelvis and =a zide diuretic, calcium channel blocker (CCB), ACE inhibitor, 2 are responsible for the creation of staghorn calculi, which are iJ or ARB, the American Diabetes Association (ADA) recom- © stones that bridge two or more renal calyces. Because struvite wv mends an ACE inhibitor or ARB at the maximum tolerated stones are large and grow rapidly, they do not pass into the dose as first-line treatment for hypertension in patients with ureter to cause pain typical of smaller stones. Struvite stones diabetes and urine albumin-creatinine ratio >300 mg/g; form most commonly in women, and women are more likely treatment with these drugs should be initiated when the than men to develop upper UTI. Other predisposing condi- urine albumin-creatinine ratio is >30 to 300 mg/g. For this tions include urinary stasis from a neurogenic bladder, as seen reason, felodipine (a CCB) and hydrochlorothiazide (a thia- in this patient. Patients with infection caused by urea-splitting zide diuretic) are not the most appropriate initial therapies organisms have the typical signs and symptoms of UTI. How- for this patient (Options A-C). ever, these stones may become persistently infected despite Initial treatment with two antihypertensive drugs is antibiotic therapy and are a source of significant morbidity recommended for patients with stage 2 hypertension and and mortality due to sepsis. Percutaneous nephrolithotomy is who are >20/10 mm Hg above their target blood pressure. the first-line treatment for most patients. According to the ADA, this patient’s target blood pressure In 95% of cases, UTIs are caused by a single bacterial is <140/90 mm Hg or <130/80 mm Hg in the presence species, mainly gram-negative aerobic bacilli originating of atherosclerotic cardiovascular disease or if her 10-year from the bowel. Uropathogenic Escherichia coli (Option A) atherosclerotic cardiovascular disease event risk is >15%. accounts for 75% to 95% of UTIs in women. Less common Regardless, the patient is not >20/10 mm Hg above her urinary pathogens include other members of the Entero- blood pressure target, and the initiation of two antihyper- bacteriaceae family, staphylococci (most often Staphylo- tensive drugs is not indicated. However, if this patient’s coccus saprophyticus) (Option C), streptococci (in partic- blood pressure is still not controlled to target while receiving ular Streptococcus agalactiae) (Option D), and enterococci. the maximum dose of lisinopril, then another class of first- UTIs occurring in hospitals and long-term care facilities line antihypertensive agents, such as a thiazide diuretic or frequently involve a more varied group of organisms (such CCB, should be added. as Enterobacter, Providencia, Morganella, Citrobacter, Ser- ratia, and Pseudomonas). These bacteria are not associated with crystal formation. e An ACE inhibitor or angiotensin receptor blocker is the initial treatment of choice for hypertension in patients with diabetes mellitus and albuminuria. e Infection with urea-splitting organisms such as Proteus, Klebsiella, and Pseudomonas increases urine e Use of an ACE inhibitor or angiotensin receptor pH and results in the precipitation of magnesium blocker can result in decreased progression of albu- ammonium phosphate, also known as struvite. minuria and chronic kidney disease in patients with diabetes mellitus and albuminuria. ¢ Struvite crystals in the urine are recognized by their characteristic coffin-lid appearance.

The most appropriate initial therapy is lisinopril (Option D), an Item 38 Answer: B ACE inhibitor, to treat hypertension in this patient with type Educational Objective: Diagnose urinary tract infection 2 diabetes mellitus and albuminuria. Although this patient’s caused by a urea-splitting organism. serum creatinine level is normal, she has evidence of chronic kidney disease (CKD) based on the presence of albuminuria Proteus mirabilis (Option B) is the most likely organism (urine albumin-creatinine ratio >30 mg/g). Albuminuria and responsible for this patient’s infection. This patient most likely uncontrolled blood pressure increase her risk for progression has a urinary tract infection (UTI) caused by Proteus, or other of CKD. Several large randomized controlled trials showed urea-splitting organisms such as Klebsiella or, less frequently, = that use of an ACE inhibitor or angiotensin receptor blocker Pseudomonas. These bacteria secrete urease, which enzymat- = (ARB) can result in decreased progression of albuminuria na ically hydrolyzes urea into carbon dioxide and ammonium, = and CKD, which may include doubling of serum creatinine @ which markedly increases urine pH and results in the pre- od or progression to end-stage kidney disease, in patients with wn cipitation of magnesium ammonium phosphate, also known So diabetes and albuminuria. = as struvite. On urinalysis, the urine pH will be >7.5. Struvite Qa. Although first-line antihypertensive therapy in non- crystals are recognized by their coffin-lid appearance. Struvite a Black patients in the absence of proteinuria includes a thia- oe crystals can rapidly form large stones in the renal pelvis and =a zide diuretic, calcium channel blocker (CCB), ACE inhibitor, 2 are responsible for the creation of staghorn calculi, which are iJ or ARB, the American Diabetes Association (ADA) recom- © stones that bridge two or more renal calyces. Because struvite wv mends an ACE inhibitor or ARB at the maximum tolerated stones are large and grow rapidly, they do not pass into the dose as first-line treatment for hypertension in patients with ureter to cause pain typical of smaller stones. Struvite stones diabetes and urine albumin-creatinine ratio >300 mg/g; form most commonly in women, and women are more likely treatment with these drugs should be initiated when the than men to develop upper UTI. Other predisposing condi- urine albumin-creatinine ratio is >30 to 300 mg/g. For this tions include urinary stasis from a neurogenic bladder, as seen reason, felodipine (a CCB) and hydrochlorothiazide (a thia- in this patient. Patients with infection caused by urea-splitting zide diuretic) are not the most appropriate initial therapies organisms have the typical signs and symptoms of UTI. How- for this patient (Options A-C). ever, these stones may become persistently infected despite Initial treatment with two antihypertensive drugs is antibiotic therapy and are a source of significant morbidity recommended for patients with stage 2 hypertension and and mortality due to sepsis. Percutaneous nephrolithotomy is who are >20/10 mm Hg above their target blood pressure. the first-line treatment for most patients. According to the ADA, this patient’s target blood pressure In 95% of cases, UTIs are caused by a single bacterial is <140/90 mm Hg or <130/80 mm Hg in the presence species, mainly gram-negative aerobic bacilli originating of atherosclerotic cardiovascular disease or if her 10-year from the bowel. Uropathogenic Escherichia coli (Option A) atherosclerotic cardiovascular disease event risk is >15%. accounts for 75% to 95% of UTIs in women. Less common Regardless, the patient is not >20/10 mm Hg above her urinary pathogens include other members of the Entero- blood pressure target, and the initiation of two antihyper- bacteriaceae family, staphylococci (most often Staphylo- tensive drugs is not indicated. However, if this patient’s coccus saprophyticus) (Option C), streptococci (in partic- blood pressure is still not controlled to target while receiving ular Streptococcus agalactiae) (Option D), and enterococci. the maximum dose of lisinopril, then another class of first- UTIs occurring in hospitals and long-term care facilities line antihypertensive agents, such as a thiazide diuretic or frequently involve a more varied group of organisms (such CCB, should be added. as Enterobacter, Providencia, Morganella, Citrobacter, Ser- ratia, and Pseudomonas). These bacteria are not associated with crystal formation. e An ACE inhibitor or angiotensin receptor blocker is the initial treatment of choice for hypertension in patients with diabetes mellitus and albuminuria. e Infection with urea-splitting organisms such as Proteus, Klebsiella, and Pseudomonas increases urine e Use of an ACE inhibitor or angiotensin receptor pH and results in the precipitation of magnesium blocker can result in decreased progression of albu- ammonium phosphate, also known as struvite. minuria and chronic kidney disease in patients with diabetes mellitus and albuminuria. ¢ Struvite crystals in the urine are recognized by their characteristic coffin-lid appearance. Bibliography Bibliography American Diabetes Association. 10. Cardiovascular disease and risk man- Daudon M, Frochot V. Crystalluria. Clin Chem Lab Med. 2015;53 Suppl agement: standards of medical care in diabetes-2021. Diabetes Care. 2:81479-87. [PMID: 26509782] doi:10.1515/eclm-2015-0860 2021;44:S125-S150. [PMID: 33298421] doi:10.2337/de21-S010

Bibliography Bibliography American Diabetes Association. 10. Cardiovascular disease and risk man- Daudon M, Frochot V. Crystalluria. Clin Chem Lab Med. 2015;53 Suppl agement: standards of medical care in diabetes-2021. Diabetes Care. 2:81479-87. [PMID: 26509782] doi:10.1515/eclm-2015-0860 2021;44:S125-S150. [PMID: 33298421] doi:10.2337/de21-S010 140

Answers and Critiques Item 40 Answer: A Bibliography Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of Educational Objective: Manage nephrogenic diabetes nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015;11:576-588. insipidus. [PMID: 26077742] doi:10.1038/nrneph.2015.89

Item 40 Answer: A Bibliography Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of Educational Objective: Manage nephrogenic diabetes nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015;11:576-588. insipidus. [PMID: 26077742] doi:10.1038/nrneph.2015.89 The most appropriate management is to add amiloride (Option A). This patient has polyuria, a serum sodium con- centration at the upper limit of normal, and dilute urine, Item 41 Answer: D which establish the diagnosis of diabetes insipidus (DI). DI Educational Objective: Manage gross hematuria in IgA may be secondary to either an inadequate release of anti- nephropathy. diuretic hormone (ADH) (central DI) or inadequate action The most appropriate management is clinical observation of ADH (nephrogenic DI). Central DI can result from tumors (Option D). This patient can be reassured that the gross hema- that invade the hypothalamus, infiltrating diseases such as turia is related to his underlying IgA nephropathy and will sarcoidosis, or surgical destruction. Nephrogenic DI is often ww resolve spontaneously. Recurrent gross hematuria, in which ct} caused by drugs such as lithium. The temporal association 3 the hematuria occurs in the setting of an upper respiratory with the initiation of lithium in this patient establishes the = infection (synpharyngitic hematuria) or after heavy exertion, diagnosis of lithium-induced nephrogenic DI. Up to 40% of - is a common manifestation of IgA nephropathy in younger rs) patients treated with lithium will develop polydipsia second- | patients; it usually portends a benign clinical course with = ary to lithium interfering with the action of ADH. Amiloride is © recurrent episodes of gross hematuria without progression the most appropriate management in this case, as it blocks the a) to chronic kidney disease. Other predictors of a benign prog- Thea

The most appropriate management is to add amiloride (Option A). This patient has polyuria, a serum sodium con- centration at the upper limit of normal, and dilute urine, Item 41 Answer: D which establish the diagnosis of diabetes insipidus (DI). DI Educational Objective: Manage gross hematuria in IgA may be secondary to either an inadequate release of anti- nephropathy. diuretic hormone (ADH) (central DI) or inadequate action The most appropriate management is clinical observation of ADH (nephrogenic DI). Central DI can result from tumors (Option D). This patient can be reassured that the gross hema- that invade the hypothalamus, infiltrating diseases such as turia is related to his underlying IgA nephropathy and will sarcoidosis, or surgical destruction. Nephrogenic DI is often ww resolve spontaneously. Recurrent gross hematuria, in which ct} caused by drugs such as lithium. The temporal association 3 the hematuria occurs in the setting of an upper respiratory with the initiation of lithium in this patient establishes the = infection (synpharyngitic hematuria) or after heavy exertion, diagnosis of lithium-induced nephrogenic DI. Up to 40% of - is a common manifestation of IgA nephropathy in younger rs) patients treated with lithium will develop polydipsia second- | patients; it usually portends a benign clinical course with = ary to lithium interfering with the action of ADH. Amiloride is © recurrent episodes of gross hematuria without progression the most appropriate management in this case, as it blocks the a) to chronic kidney disease. Other predictors of a benign prog- Thea epithelial sodium channel in the collecting tubule and pre- o nosis include a normal serum creatinine concentration and = vents the uptake of lithium by these cells. Intracellular lithium wn blood pressure as well as minimal proteinuria. eS appears to decrease the number of aquaporin water channels <x Amoxicillin (Option A) would be indicated to treat strep- inserted in the membrane, thereby decreasing water reab- tococcal pharyngitis. However, this diagnosis is unlikely in the sorption causing increased excretion of dilute urine. If ami- presence of cough, the absence of pharyngeal exudate and loride is ineffective and lithium must be continued, the treat- cervical lymphadenopathy, and a negative rapid antigen test. ment of nephrogenic DI is aimed at decreasing the amount CT of the abdomen and pelvis (Option B) is an appro- of urine excreted and is best accomplished by limiting solute priate screening test for unexplained gross hematuria, which intake and causing mild volume depletion with the use of a may be due to the presence of a stone or mass in the kidney thiazide diuretic. Because the amount of urine excreted daily or bladder. However, this patient has a known diagnosis of is dependent on solute intake and minimum urine osmolality, IgA nephropathy and a classic presentation of synpharyn- decreasing solute will limit urine volume. By causing mild gitic hematuria; the gross hematuria is well explained, and volume depletion with a thiazide diuretic, more salt and water imaging is not required. will be reabsorbed in the proximal tubule and loop of Henle, Glucocorticoid therapy, such as with prednisone further decreasing urine output. (Option C), is unnecessary in a mild form of nonprogressive Although furosemide (Option B) will produce volume IgA nephropathy. The use of immunosuppression in pro- depletion, it is not helpful in the treatment of nephrogenic DI. gressive IgA nephropathy remains controversial: The STOP- Furosemide blocks the ability to concentrate the urine at the IgAN study showed no benefit of glucocorticoid therapy in loop of Henle, creating a state of antidiuretic hormone resistance. slowing the decline of kidney function, and the TESTING Patients with nephrogenic DI will develop increased study was terminated early due to significantly increased thirst as their serum sodium increases. Water intake should risk for adverse events in patients treated with glucocorti- never be restricted (Option C) in patients with nephrogenic coids. Therefore, glucocorticoid therapy is reserved for severe DI because it can lead to severe hypernatremia. forms of IgA nephropathy deemed high risk for rapid pro- Because the treatment of nephrogenic DI is aimed at gression to end-stage kidney disease. decreasing solute intake, increasing protein intake (Option D) is not appropriate management.

epithelial sodium channel in the collecting tubule and pre- o nosis include a normal serum creatinine concentration and = vents the uptake of lithium by these cells. Intracellular lithium wn blood pressure as well as minimal proteinuria. eS appears to decrease the number of aquaporin water channels <x Amoxicillin (Option A) would be indicated to treat strep- inserted in the membrane, thereby decreasing water reab- tococcal pharyngitis. However, this diagnosis is unlikely in the sorption causing increased excretion of dilute urine. If ami- presence of cough, the absence of pharyngeal exudate and loride is ineffective and lithium must be continued, the treat- cervical lymphadenopathy, and a negative rapid antigen test. ment of nephrogenic DI is aimed at decreasing the amount CT of the abdomen and pelvis (Option B) is an appro- of urine excreted and is best accomplished by limiting solute priate screening test for unexplained gross hematuria, which intake and causing mild volume depletion with the use of a may be due to the presence of a stone or mass in the kidney thiazide diuretic. Because the amount of urine excreted daily or bladder. However, this patient has a known diagnosis of is dependent on solute intake and minimum urine osmolality, IgA nephropathy and a classic presentation of synpharyn- decreasing solute will limit urine volume. By causing mild gitic hematuria; the gross hematuria is well explained, and volume depletion with a thiazide diuretic, more salt and water imaging is not required. will be reabsorbed in the proximal tubule and loop of Henle, Glucocorticoid therapy, such as with prednisone further decreasing urine output. (Option C), is unnecessary in a mild form of nonprogressive Although furosemide (Option B) will produce volume IgA nephropathy. The use of immunosuppression in pro- depletion, it is not helpful in the treatment of nephrogenic DI. gressive IgA nephropathy remains controversial: The STOP- Furosemide blocks the ability to concentrate the urine at the IgAN study showed no benefit of glucocorticoid therapy in loop of Henle, creating a state of antidiuretic hormone resistance. slowing the decline of kidney function, and the TESTING Patients with nephrogenic DI will develop increased study was terminated early due to significantly increased thirst as their serum sodium increases. Water intake should risk for adverse events in patients treated with glucocorti- never be restricted (Option C) in patients with nephrogenic coids. Therefore, glucocorticoid therapy is reserved for severe DI because it can lead to severe hypernatremia. forms of IgA nephropathy deemed high risk for rapid pro- Because the treatment of nephrogenic DI is aimed at gression to end-stage kidney disease. decreasing solute intake, increasing protein intake (Option D) is not appropriate management. ¢ In younger patients with IgA nephropathy, recurrent hematuria in the absence of proteinuria usually portends ¢ Treatment of lithium-induced nephrogenic diabetes a benign clinical course and treatment is conservative. insipidus is best accomplished with amiloride, as it e Recurrent gross hematuria, often occurring at the blocks the epithelial sodium channel in the collecting time of an upper respiratory infection or following tubule and prevents the uptake of lithium by these cells. strenuous exercise, is a common manifestation of IgA ¢ If amiloride is ineffective in treating lithium-induced nephropathy in younger patients. nephrogenic diabetes insipidus and lithium must be continued, treatment is aimed at limiting solute Bibliography intake and causing mild volume depletion with the Schena FP, Nistor I. Epidemiology of IgA nephropathy: a global perspective. use of a thiazide diuretic. Semin Nephrol. 2018;38:435-42. [PMID: 30177015] doi:10.1016/j. semnephrol.2018.05.013

¢ In younger patients with IgA nephropathy, recurrent hematuria in the absence of proteinuria usually portends ¢ Treatment of lithium-induced nephrogenic diabetes a benign clinical course and treatment is conservative. insipidus is best accomplished with amiloride, as it e Recurrent gross hematuria, often occurring at the blocks the epithelial sodium channel in the collecting time of an upper respiratory infection or following tubule and prevents the uptake of lithium by these cells. strenuous exercise, is a common manifestation of IgA ¢ If amiloride is ineffective in treating lithium-induced nephropathy in younger patients. nephrogenic diabetes insipidus and lithium must be continued, treatment is aimed at limiting solute Bibliography intake and causing mild volume depletion with the Schena FP, Nistor I. Epidemiology of IgA nephropathy: a global perspective. use of a thiazide diuretic. Semin Nephrol. 2018;38:435-42. [PMID: 30177015] doi:10.1016/j. semnephrol.2018.05.013 141

Answers and Critiques Item 42 Answer: D Item 43 Answer: A Educational Objective: Manage vaccinations in a Educational Objective: Diagnose contrast-associated patient with chronic kidney disease. acute tubular necrosis. The most appropriate additional vaccine to administer at The most likely diagnosis is acute tubular necrosis (ATN) this visit is the pneumococcal conjugate vaccine (Option D). (Option A) due to contrast-associated nephropathy (CAN). Chronic kidney disease (CKD) is an indication for pneumococ- CAN is characterized by an abrupt increase in the serum cal vaccination. Two pneumococcal vaccines are available: the creatinine level 24 to 48 hours after contrast exposure. This 13-valent pneumococcal conjugate vaccine (PCV13) and the patient’s risk factors for CAN include chronic kidney injury, 23-valent pneumococcal polysaccharide vaccine (PPSV23). type 2 diabetes mellitus, and a presumptive large volume In adults aged 19 to 64 years with CKD, vaccination with contrast exposure. Laboratory findings consistent with the both PCV13 and PPSV23 is indicated. For patients who have diagnosis include a blood urea nitrogen (BUN)-creatinine

The most appropriate additional vaccine to administer at The most likely diagnosis is acute tubular necrosis (ATN) this visit is the pneumococcal conjugate vaccine (Option D). (Option A) due to contrast-associated nephropathy (CAN). Chronic kidney disease (CKD) is an indication for pneumococ- CAN is characterized by an abrupt increase in the serum cal vaccination. Two pneumococcal vaccines are available: the creatinine level 24 to 48 hours after contrast exposure. This 13-valent pneumococcal conjugate vaccine (PCV13) and the patient’s risk factors for CAN include chronic kidney injury, 23-valent pneumococcal polysaccharide vaccine (PPSV23). type 2 diabetes mellitus, and a presumptive large volume In adults aged 19 to 64 years with CKD, vaccination with contrast exposure. Laboratory findings consistent with the both PCV13 and PPSV23 is indicated. For patients who have diagnosis include a blood urea nitrogen (BUN)-creatinine PI not yet received either vaccine, a single dose of PCV13 should ratio of 15:1, urine specific gravity of 1.010 (isosthenuria), = urine sodium >40 mEq/L (40 mmol/L), and a urine sediment nn be given first, followed by a single dose of PPSV23 given at = least 8 weeks later. In this patient, a second dose of PPSV23 with a few granular casts; notably, pigmented granular casts © ~ wi should also be administered 5 years after the first PPSV23 dose do not have to be present to diagnose ATN. ao (Option E). In addition, patients with CKD and end-stage kid- Atheroembolic-induced acute kidney injury (Option = a. ney disease (ESKD) are at increased risk for influenza-related B) after a vascular intervention is characterized by a slow, “ morbidity and mortality and should be strongly encouraged to stuttering rise in the serum creatinine level, often not appar- =e =. receive the influenza vaccine annually. Influenza vaccination ent until several days or weeks after the procedure. It is x =7 | J has been shown to decrease influenza-related mortality and often accompanied by stigmata of atheroemboli to the lower © wn decrease hospitalization for acute coronary syndrome and extremities, including livedo reticularis. In this patient, heart failure in patients who are vaccinated. serum creatinine levels began rising 24 hours after the pro- Patients with CKD and ESKD should receive vaccines cedure and he has no skin findings. for hepatitis A or herpes zoster (shingles) (Options A, C) and Clopidogrel can be a cause of hemolytic uremic syn- others (for example, tetanus toxoid, reduced diphtheria tox- drome (Option C). However, this syndrome is typically char- oid, and acellular pertussis) according to the same guidelines acterized by a profound decrease in hemoglobin levels and as the general population based on age (+50 years) for the platelet counts, and a longer exposure to the offending agent herpes zoster vaccine and hepatitis A vaccine for upcoming would be expected before the full manifestations develop. In travel to endemic areas, and for adults at risk for hepatitis A this patient, the anemia and thrombocytopenia are modest virus (HAV) infection or severe disease from HAV infection and nonspecific. and for adults requesting protection against HAV without Prerenal acute kidney injury (Option D) is unlikely in acknowledgment of a risk factor. the absence of physical findings supporting hypovolemia Patients with ESKD who are receiving hemodialysis or reduced cardiac output. Additionally, BUN-creatinine and blood transfusions are at increased risk for exposure ratio >20:1, urine specific gravity >1.020, and a normal to blood-borne viruses. Hepatitis B vaccination (Option B) microscopic urinalysis or presence of hyaline casts are more is indicated for patients with CKD who are not already typical. immune. For patients on hemodialysis, the vaccine should be administered as part of the infection control program at the dialysis center. Patients with ESKD require a higher dose ¢ Contrast-associated nephropathy is a cause of acute

PI not yet received either vaccine, a single dose of PCV13 should ratio of 15:1, urine specific gravity of 1.010 (isosthenuria), = urine sodium >40 mEq/L (40 mmol/L), and a urine sediment nn be given first, followed by a single dose of PPSV23 given at = least 8 weeks later. In this patient, a second dose of PPSV23 with a few granular casts; notably, pigmented granular casts © ~ wi should also be administered 5 years after the first PPSV23 dose do not have to be present to diagnose ATN. ao (Option E). In addition, patients with CKD and end-stage kid- Atheroembolic-induced acute kidney injury (Option = a. ney disease (ESKD) are at increased risk for influenza-related B) after a vascular intervention is characterized by a slow, “ morbidity and mortality and should be strongly encouraged to stuttering rise in the serum creatinine level, often not appar- =e =. receive the influenza vaccine annually. Influenza vaccination ent until several days or weeks after the procedure. It is x =7 | J has been shown to decrease influenza-related mortality and often accompanied by stigmata of atheroemboli to the lower © wn decrease hospitalization for acute coronary syndrome and extremities, including livedo reticularis. In this patient, heart failure in patients who are vaccinated. serum creatinine levels began rising 24 hours after the pro- Patients with CKD and ESKD should receive vaccines cedure and he has no skin findings. for hepatitis A or herpes zoster (shingles) (Options A, C) and Clopidogrel can be a cause of hemolytic uremic syn- others (for example, tetanus toxoid, reduced diphtheria tox- drome (Option C). However, this syndrome is typically char- oid, and acellular pertussis) according to the same guidelines acterized by a profound decrease in hemoglobin levels and as the general population based on age (+50 years) for the platelet counts, and a longer exposure to the offending agent herpes zoster vaccine and hepatitis A vaccine for upcoming would be expected before the full manifestations develop. In travel to endemic areas, and for adults at risk for hepatitis A this patient, the anemia and thrombocytopenia are modest virus (HAV) infection or severe disease from HAV infection and nonspecific. and for adults requesting protection against HAV without Prerenal acute kidney injury (Option D) is unlikely in acknowledgment of a risk factor. the absence of physical findings supporting hypovolemia Patients with ESKD who are receiving hemodialysis or reduced cardiac output. Additionally, BUN-creatinine and blood transfusions are at increased risk for exposure ratio >20:1, urine specific gravity >1.020, and a normal to blood-borne viruses. Hepatitis B vaccination (Option B) microscopic urinalysis or presence of hyaline casts are more is indicated for patients with CKD who are not already typical. immune. For patients on hemodialysis, the vaccine should be administered as part of the infection control program at the dialysis center. Patients with ESKD require a higher dose ¢ Contrast-associated nephropathy is a cause of acute of vaccine to enhance the likelihood of immune response. tubular necrosis and is characterized by an increase in

PI not yet received either vaccine, a single dose of PCV13 should ratio of 15:1, urine specific gravity of 1.010 (isosthenuria), = urine sodium >40 mEq/L (40 mmol/L), and a urine sediment nn be given first, followed by a single dose of PPSV23 given at = least 8 weeks later. In this patient, a second dose of PPSV23 with a few granular casts; notably, pigmented granular casts © ~ wi should also be administered 5 years after the first PPSV23 dose do not have to be present to diagnose ATN. ao (Option E). In addition, patients with CKD and end-stage kid- Atheroembolic-induced acute kidney injury (Option = a. ney disease (ESKD) are at increased risk for influenza-related B) after a vascular intervention is characterized by a slow, “ morbidity and mortality and should be strongly encouraged to stuttering rise in the serum creatinine level, often not appar- =e =. receive the influenza vaccine annually. Influenza vaccination ent until several days or weeks after the procedure. It is x =7 | J has been shown to decrease influenza-related mortality and often accompanied by stigmata of atheroemboli to the lower © wn decrease hospitalization for acute coronary syndrome and extremities, including livedo reticularis. In this patient, heart failure in patients who are vaccinated. serum creatinine levels began rising 24 hours after the pro- Patients with CKD and ESKD should receive vaccines cedure and he has no skin findings. for hepatitis A or herpes zoster (shingles) (Options A, C) and Clopidogrel can be a cause of hemolytic uremic syn- others (for example, tetanus toxoid, reduced diphtheria tox- drome (Option C). However, this syndrome is typically char- oid, and acellular pertussis) according to the same guidelines acterized by a profound decrease in hemoglobin levels and as the general population based on age (+50 years) for the platelet counts, and a longer exposure to the offending agent herpes zoster vaccine and hepatitis A vaccine for upcoming would be expected before the full manifestations develop. In travel to endemic areas, and for adults at risk for hepatitis A this patient, the anemia and thrombocytopenia are modest virus (HAV) infection or severe disease from HAV infection and nonspecific. and for adults requesting protection against HAV without Prerenal acute kidney injury (Option D) is unlikely in acknowledgment of a risk factor. the absence of physical findings supporting hypovolemia Patients with ESKD who are receiving hemodialysis or reduced cardiac output. Additionally, BUN-creatinine and blood transfusions are at increased risk for exposure ratio >20:1, urine specific gravity >1.020, and a normal to blood-borne viruses. Hepatitis B vaccination (Option B) microscopic urinalysis or presence of hyaline casts are more is indicated for patients with CKD who are not already typical. immune. For patients on hemodialysis, the vaccine should be administered as part of the infection control program at the dialysis center. Patients with ESKD require a higher dose ¢ Contrast-associated nephropathy is a cause of acute of vaccine to enhance the likelihood of immune response. tubular necrosis and is characterized by an increase in Serology indicates that this patient is immune to hepatitis B; the serum creatinine 24 to 48 hours after contrast

PI not yet received either vaccine, a single dose of PCV13 should ratio of 15:1, urine specific gravity of 1.010 (isosthenuria), = urine sodium >40 mEq/L (40 mmol/L), and a urine sediment nn be given first, followed by a single dose of PPSV23 given at = least 8 weeks later. In this patient, a second dose of PPSV23 with a few granular casts; notably, pigmented granular casts © ~ wi should also be administered 5 years after the first PPSV23 dose do not have to be present to diagnose ATN. ao (Option E). In addition, patients with CKD and end-stage kid- Atheroembolic-induced acute kidney injury (Option = a. ney disease (ESKD) are at increased risk for influenza-related B) after a vascular intervention is characterized by a slow, “ morbidity and mortality and should be strongly encouraged to stuttering rise in the serum creatinine level, often not appar- =e =. receive the influenza vaccine annually. Influenza vaccination ent until several days or weeks after the procedure. It is x =7 | J has been shown to decrease influenza-related mortality and often accompanied by stigmata of atheroemboli to the lower © wn decrease hospitalization for acute coronary syndrome and extremities, including livedo reticularis. In this patient, heart failure in patients who are vaccinated. serum creatinine levels began rising 24 hours after the pro- Patients with CKD and ESKD should receive vaccines cedure and he has no skin findings. for hepatitis A or herpes zoster (shingles) (Options A, C) and Clopidogrel can be a cause of hemolytic uremic syn- others (for example, tetanus toxoid, reduced diphtheria tox- drome (Option C). However, this syndrome is typically char- oid, and acellular pertussis) according to the same guidelines acterized by a profound decrease in hemoglobin levels and as the general population based on age (+50 years) for the platelet counts, and a longer exposure to the offending agent herpes zoster vaccine and hepatitis A vaccine for upcoming would be expected before the full manifestations develop. In travel to endemic areas, and for adults at risk for hepatitis A this patient, the anemia and thrombocytopenia are modest virus (HAV) infection or severe disease from HAV infection and nonspecific. and for adults requesting protection against HAV without Prerenal acute kidney injury (Option D) is unlikely in acknowledgment of a risk factor. the absence of physical findings supporting hypovolemia Patients with ESKD who are receiving hemodialysis or reduced cardiac output. Additionally, BUN-creatinine and blood transfusions are at increased risk for exposure ratio >20:1, urine specific gravity >1.020, and a normal to blood-borne viruses. Hepatitis B vaccination (Option B) microscopic urinalysis or presence of hyaline casts are more is indicated for patients with CKD who are not already typical. immune. For patients on hemodialysis, the vaccine should be administered as part of the infection control program at the dialysis center. Patients with ESKD require a higher dose ¢ Contrast-associated nephropathy is a cause of acute of vaccine to enhance the likelihood of immune response. tubular necrosis and is characterized by an increase in Serology indicates that this patient is immune to hepatitis B; the serum creatinine 24 to 48 hours after contrast therefore, vaccination is not indicated. exposure.

of vaccine to enhance the likelihood of immune response. tubular necrosis and is characterized by an increase in Serology indicates that this patient is immune to hepatitis B; the serum creatinine 24 to 48 hours after contrast therefore, vaccination is not indicated. exposure. Bibliography e Patients with chronic kidney disease and end-stage Mehran R, Dangas GD, Weisbord SD. Contrast-associated acute kidney kidney disease or on hemodialysis should receive both injury. N EnglJ Med. 2019;380:2146-2155. [PMID: 31141635] doi:10.1056/ NEJMral1805256 pneumococcal vaccines. e Patients with chronic kidney disease and end-stage kid- ney disease are at increased risk for influenza-related Item 44 Answer: D morbidity and mortality and should receive the influ- Educational Objective: Treat salicylate toxicity. enza vaccine annually. The most appropriate treatment is intravenous sodium bicar- Bibliography bonate (Option D). This patient has salicylate toxicity related Krueger KM, Ison MG, Ghossein C. Practical guide to vaccination in all to the ingestion of aspirin and has developed a complex stages of CKD, including patients treated by dialysis or kidney transplan- mixed acid-base disorder characterized by respiratory alka- tation. AmJ Kidney Dis. 2020;75:417-425. [PMID: 31585683] doi:10.1053 /j. ajkd.2019.06.014 losis, increased anion gap metabolic acidosis, and metabolic 142

Answers and Critiques alkalosis. Intravenous sodium bicarbonate administration as obligatory entry criterion, followed by additive weighted increases urinary elimination of salicylate (with a goal of a criteria grouped into seven clinical and three immunologic co NT. urine pH >7.5) and protects the patient from central nervous domains. Patients with the entry criteria of a positive ANA, system (CNS) toxicity. Maintaining the serum pH at 7.50 to at least one clinical criterion, and having accumulated 210 7.55 is essential to avoid CNS accumulation of salicylic acid in points are classified as having SLE with a sensitivity of 96.1% the brain. Aspirin (acetylsalicylic acid) is rapidly converted to and specificity of 93.4%. This patient has a positive ANA, acute salicylic acid in the body. Acidosis promotes the influx of sali- cutaneous lupus erythematosus, and low serum complement cylic acid into the CNS. Increasing the systemic pH with alkali levels (10 total points). The classic pattern of lupus nephritis therapy favors the formation of the ionic form of salicylic acid is an immune complex-mediated glomerulonephritis with a where it is “trapped” in extracellular fluid. The formation of varied pathology that includes six distinct classes of disease. ionic salicylic acid in extracellular fluid creates a favorable The biopsy is crucial not only to establish the diagnosis but concentration gradient for diffusion of salicylic acid from also to indicate which class of lupus nephritis she has, as the the CNS to the extracellular fluid. Alkalinization of the urine approach to treating lupus nephritis is guided by histologic w” o converts urinary salicylic acid to its ionic form, trapping it in class and the degree of kidney function impairment. s zo the renal tubule and diminishing the diffusion from the renal Erythrocyte sedimentation rate (ESR) (Option A) mea- = tubule back into the systemic circulation. surement can be checked serially alongside other clinical ‘= s) Acetazolamide (Option A) is not indicated in the treat- parameters to gauge disease activity. However, an ESR mea- =) < ment of salicylate toxicity. Although acetazolamide, a car- surement would not help in determining the class of lupus Cc

alkalosis. Intravenous sodium bicarbonate administration as obligatory entry criterion, followed by additive weighted increases urinary elimination of salicylate (with a goal of a criteria grouped into seven clinical and three immunologic co NT. urine pH >7.5) and protects the patient from central nervous domains. Patients with the entry criteria of a positive ANA, system (CNS) toxicity. Maintaining the serum pH at 7.50 to at least one clinical criterion, and having accumulated 210 7.55 is essential to avoid CNS accumulation of salicylic acid in points are classified as having SLE with a sensitivity of 96.1% the brain. Aspirin (acetylsalicylic acid) is rapidly converted to and specificity of 93.4%. This patient has a positive ANA, acute salicylic acid in the body. Acidosis promotes the influx of sali- cutaneous lupus erythematosus, and low serum complement cylic acid into the CNS. Increasing the systemic pH with alkali levels (10 total points). The classic pattern of lupus nephritis therapy favors the formation of the ionic form of salicylic acid is an immune complex-mediated glomerulonephritis with a where it is “trapped” in extracellular fluid. The formation of varied pathology that includes six distinct classes of disease. ionic salicylic acid in extracellular fluid creates a favorable The biopsy is crucial not only to establish the diagnosis but concentration gradient for diffusion of salicylic acid from also to indicate which class of lupus nephritis she has, as the the CNS to the extracellular fluid. Alkalinization of the urine approach to treating lupus nephritis is guided by histologic w” o converts urinary salicylic acid to its ionic form, trapping it in class and the degree of kidney function impairment. s zo the renal tubule and diminishing the diffusion from the renal Erythrocyte sedimentation rate (ESR) (Option A) mea- = tubule back into the systemic circulation. surement can be checked serially alongside other clinical ‘= s) Acetazolamide (Option A) is not indicated in the treat- parameters to gauge disease activity. However, an ESR mea- =) < ment of salicylate toxicity. Although acetazolamide, a car- surement would not help in determining the class of lupus Cc bonic anhydrase inhibitor, can alkalinize the urine, it does nephritis needed to choose optimal therapy. ww coal o so by reducing bicarbonate reabsorption. The alkaline urine This patient may test positive for one or more antibodies = will result in enhanced excretion of salicylic acid; however, on the extractable nuclear antigen (ENA) (Option B) panel wh = the loss of bicarbonate will result in a mild systemic acidosis (e.g., anti-Smith, anti-U1-RNP, anti-Ro/SSA, anti-La/SSB), =

bonic anhydrase inhibitor, can alkalinize the urine, it does nephritis needed to choose optimal therapy. ww coal o so by reducing bicarbonate reabsorption. The alkaline urine This patient may test positive for one or more antibodies = will result in enhanced excretion of salicylic acid; however, on the extractable nuclear antigen (ENA) (Option B) panel wh = the loss of bicarbonate will result in a mild systemic acidosis (e.g., anti-Smith, anti-U1-RNP, anti-Ro/SSA, anti-La/SSB), = and will drive salicylate into the CNS. but this antibody panel test is not required to make a diag- Hemodialysis (Option B) is not indicated for this patient. nosis of SLE. In addition, the results of an ENA panel are not It is indicated for patients with serum salicylate levels >90 to expected to influence treatment plans compared with those 100 pg/mL (651-724 umol/L) with acute intoxication and of a kidney biopsy. >60 ug/mL (434.4 umol/L) in chronic administration, or if The diagnosis of acute cutaneous lupus erythemato- there is acute kidney injury, cerebral or pulmonary edema, sus is primarily clinical. A skin biopsy (Option D) is indi- refractory acidemia, or severe alteration of mental status. cated when the clinical diagnosis is in doubt. In this case, Forced diuresis with administration of intravenous the appearance of the classic malar rash in the context 0.9% saline (Option C) has no role in managing salicylate of positive SLE-associated immunologic findings make toxicity, as it will not increase elimination of salicylate in the a skin biopsy unnecessary. Finally, a skin biopsy would absence of systemic and urinary alkalinization. not shed any light on the patient’s kidney manifestations or guide therapy for either the patient’s skin or kidney disease. e Salicylate toxicity related to the ingestion of aspirin commonly manifests as a primary respiratory alkalosis or complex mixed acid-base disorders. e Kidney biopsy is the definitive diagnostic test for

and will drive salicylate into the CNS. but this antibody panel test is not required to make a diag- Hemodialysis (Option B) is not indicated for this patient. nosis of SLE. In addition, the results of an ENA panel are not It is indicated for patients with serum salicylate levels >90 to expected to influence treatment plans compared with those 100 pg/mL (651-724 umol/L) with acute intoxication and of a kidney biopsy. >60 ug/mL (434.4 umol/L) in chronic administration, or if The diagnosis of acute cutaneous lupus erythemato- there is acute kidney injury, cerebral or pulmonary edema, sus is primarily clinical. A skin biopsy (Option D) is indi- refractory acidemia, or severe alteration of mental status. cated when the clinical diagnosis is in doubt. In this case, Forced diuresis with administration of intravenous the appearance of the classic malar rash in the context 0.9% saline (Option C) has no role in managing salicylate of positive SLE-associated immunologic findings make toxicity, as it will not increase elimination of salicylate in the a skin biopsy unnecessary. Finally, a skin biopsy would absence of systemic and urinary alkalinization. not shed any light on the patient’s kidney manifestations or guide therapy for either the patient’s skin or kidney disease. e Salicylate toxicity related to the ingestion of aspirin commonly manifests as a primary respiratory alkalosis or complex mixed acid-base disorders. e Kidney biopsy is the definitive diagnostic test for lupus nephritis and, based on histologic findings, is e Intravenous sodium bicarbonate administration is used crucial in determining treatment. to treat patients with salicylate toxicity, as it increases urinary elimination of salicylate (with a goal of a urine Bibliography pH 57.5) and protects the patient from central nervous Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc system toxicity. Nephrol. 2017;12:825-35. [PMID: 27821390] doi:10.2215/CJN.05780616

lupus nephritis and, based on histologic findings, is e Intravenous sodium bicarbonate administration is used crucial in determining treatment. to treat patients with salicylate toxicity, as it increases urinary elimination of salicylate (with a goal of a urine Bibliography pH 57.5) and protects the patient from central nervous Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc system toxicity. Nephrol. 2017;12:825-35. [PMID: 27821390] doi:10.2215/CJN.05780616 Bibliography Palmer BE, Clegg DJ. Salicylate toxicity. N Engl J Med. 2020;382(26):2544- Item 46 Answer: D 2555. [PMID: 32579814] doi:10.1056/NEJMra2010852 Educational Objective: Prepare a patient for end-stage kidney disease by providing renal replacement therapy education. Item 45 Answer: C This most appropriate management is renal replacement ther- Educational Objective: Diagnose lupus nephritis. apy (RRT) education (Option D). This patient with slowly pro- Kidney biopsy (Option C) is the most appropriate diagnos- gressive chronic kidney disease (CKD) is at borderline stage tic test to perform next. The 2019 European League Against G3/G4. When estimated glomerular filtration rate (eGFR) is Rheumatism/American College of Rheumatology classifica- <30 mL/min/1.73 m2, the patient should be referred for RRT tion criteria for systemic lupus erythematosus (SLE) include education. It is appropriate to begin the education process for having antinuclear antibody (ANA) positivity at least once the patient to learn about RRT options, including in-center

Bibliography Palmer BE, Clegg DJ. Salicylate toxicity. N Engl J Med. 2020;382(26):2544- Item 46 Answer: D 2555. [PMID: 32579814] doi:10.1056/NEJMra2010852 Educational Objective: Prepare a patient for end-stage kidney disease by providing renal replacement therapy education. Item 45 Answer: C This most appropriate management is renal replacement ther- Educational Objective: Diagnose lupus nephritis. apy (RRT) education (Option D). This patient with slowly pro- Kidney biopsy (Option C) is the most appropriate diagnos- gressive chronic kidney disease (CKD) is at borderline stage tic test to perform next. The 2019 European League Against G3/G4. When estimated glomerular filtration rate (eGFR) is Rheumatism/American College of Rheumatology classifica- <30 mL/min/1.73 m2, the patient should be referred for RRT tion criteria for systemic lupus erythematosus (SLE) include education. It is appropriate to begin the education process for having antinuclear antibody (ANA) positivity at least once the patient to learn about RRT options, including in-center 143

Answers and Critiques and home hemodialysis, peritoneal dialysis, kidney trans- showing vascular calcification. Calciphylaxis develops from plantation, and non-dialytic medical management, to make pathologic calcifications in the dermal arterioles, leading to an informed decision in the future. An RRT education session thrombosis, ischemia, and necrosis of the overlying skin. It is empowers the patient to make decisions regarding venous a painful and often life-threatening complication of ESKD and access or preemptive kidney transplant to ensure a controlled is associated with a high risk of mortality due to secondary initiation of RRT. It also helps prevents the risk for initiating infection and sepsis. Many patients with calciphylaxis have dialysis emergently. Patients who receive preparatory RRT severe secondary hyperparathyroidism and elevated calcium- education before they are diagnosed with end-stage kidney phosphorous product. However, patients such as this one disease are more likely to select a home modality for RRT, be with normalized serum calcium and phosphate levels are also listed for a kidney transplant, or receive a preemptive kidney at risk; calciphylaxis is an increasingly recognized complica- transplant and may have a mortality benefit compared with tion of ESKD in the dialysis community. There are no FDA- patients who do not receive similar education. approved treatments for calciphylaxis. However, calcimimet- > Evaluation for arteriovenous fistula (AVF) placement ics are used to suppress parathyroid hormone, and data from s wn (Option A) is indicated after the patient has learned about a large study show fewer cases of calciphylaxis among treated = RRT options and chooses to receive hemodialysis in the patients. Sodium thiosulfate, an anti-inflammatory agent, is oO = wn future. After this decision, the patient is referred for arm- also routinely used for patients with calciphylaxis. <3) s access evaluation. Patients with suitable anatomy should Leukocytoclastic vasculitis (Option B) should be con- Qa. have AVF placement well in advance of anticipated ESKD to sidered in the differential diagnosis of a nonhealing leg ulcer, is) me allow adequate maturation of the vein to allow robust blood but patients typically present with palpable purpura, not a a. flow needed for hemodialysis. rapidly advancing cutaneous ulcer, and the biopsy would 2 t=} For patients amenable to dialysis (Option B), stud- show perivenular and intramural inflammatory infiltrates @o wn ies demonstrate no benefit in starting it in asymptomatic rather than the vascular calcifications seen in this patient. patients or at a specific eGFR cutoff compared with watchful Venous stasis ulcers (Option C), a chronic skin con- waiting and initiating dialysis for symptoms or metabolic dition associated with other signs of venous insufficiency abnormalities that are refractory to medical treatment. (edema, varicosities, hyperpigmentation), are irregularly Patients should be referred to a kidney transplant cen- shaped, shallow, and often weep serous fluid. The ulcers are ter for evaluation (Option C) when the eGFR is 15 to 29 mL/ rarely necrotic. The sudden appearance of a necrotic ulcer is min/1.73 m2. Early referral is important because preemptive not indicative of a venous ulcer. kidney transplants (transplants before needing dialysis) are Although warfarin-related necrosis could cause associated with improved clinical outcomes compared with necrotic skin ulceration (Option D), it would be expected to receiving a transplant after starting dialysis. Early referral occur when the agent was initiated, often with large loading also allows adequate time to identify suitable living donors; doses, and would not show calcifications in the underlying if no living donor is available, early listing is essential to vessel walls on biopsy but rather thrombosis. begin the waiting process for a deceased-donor kidney. Referral for evaluation will be appropriate if this patient selects this mode of RRT following RRT education. ¢ Calciphylaxis (calcific uremic arteriolopathy) is char- acterized by calcifications in the dermal arterioles resulting in painful ischemic skin lesions and is an e Patients with progressive chronic kidney disease and increasingly recognized complication of end-stage an estimated glomerular filtration rate <30 mL/min/ kidney disease. 1.73 m? should be referred to a renal replacement e Many patients with calciphylaxis have severe second- therapy education program. ary hyperparathyroidism and elevated calcium- phosphorous product. Bibliography Kurella Tamura M, Li S, Chen SC, et al. Educational programs improve the preparation for dialysis and survival of patients with chronic kidney Bibliography disease. Kidney Int. 2014;85:686-692. [PMID: 24067435] doi:10.1038/ Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. ki.2013.369 2018;378:1704-1714. [PMID: 29719190] doi:10.1056/NEJMra1505292

and home hemodialysis, peritoneal dialysis, kidney trans- showing vascular calcification. Calciphylaxis develops from plantation, and non-dialytic medical management, to make pathologic calcifications in the dermal arterioles, leading to an informed decision in the future. An RRT education session thrombosis, ischemia, and necrosis of the overlying skin. It is empowers the patient to make decisions regarding venous a painful and often life-threatening complication of ESKD and access or preemptive kidney transplant to ensure a controlled is associated with a high risk of mortality due to secondary initiation of RRT. It also helps prevents the risk for initiating infection and sepsis. Many patients with calciphylaxis have dialysis emergently. Patients who receive preparatory RRT severe secondary hyperparathyroidism and elevated calcium- education before they are diagnosed with end-stage kidney phosphorous product. However, patients such as this one disease are more likely to select a home modality for RRT, be with normalized serum calcium and phosphate levels are also listed for a kidney transplant, or receive a preemptive kidney at risk; calciphylaxis is an increasingly recognized complica- transplant and may have a mortality benefit compared with tion of ESKD in the dialysis community. There are no FDA- patients who do not receive similar education. approved treatments for calciphylaxis. However, calcimimet- > Evaluation for arteriovenous fistula (AVF) placement ics are used to suppress parathyroid hormone, and data from s wn (Option A) is indicated after the patient has learned about a large study show fewer cases of calciphylaxis among treated = RRT options and chooses to receive hemodialysis in the patients. Sodium thiosulfate, an anti-inflammatory agent, is oO = wn future. After this decision, the patient is referred for arm- also routinely used for patients with calciphylaxis. <3) s access evaluation. Patients with suitable anatomy should Leukocytoclastic vasculitis (Option B) should be con- Qa. have AVF placement well in advance of anticipated ESKD to sidered in the differential diagnosis of a nonhealing leg ulcer, is) me allow adequate maturation of the vein to allow robust blood but patients typically present with palpable purpura, not a a. flow needed for hemodialysis. rapidly advancing cutaneous ulcer, and the biopsy would 2 t=} For patients amenable to dialysis (Option B), stud- show perivenular and intramural inflammatory infiltrates @o wn ies demonstrate no benefit in starting it in asymptomatic rather than the vascular calcifications seen in this patient. patients or at a specific eGFR cutoff compared with watchful Venous stasis ulcers (Option C), a chronic skin con- waiting and initiating dialysis for symptoms or metabolic dition associated with other signs of venous insufficiency abnormalities that are refractory to medical treatment. (edema, varicosities, hyperpigmentation), are irregularly Patients should be referred to a kidney transplant cen- shaped, shallow, and often weep serous fluid. The ulcers are ter for evaluation (Option C) when the eGFR is 15 to 29 mL/ rarely necrotic. The sudden appearance of a necrotic ulcer is min/1.73 m2. Early referral is important because preemptive not indicative of a venous ulcer. kidney transplants (transplants before needing dialysis) are Although warfarin-related necrosis could cause associated with improved clinical outcomes compared with necrotic skin ulceration (Option D), it would be expected to receiving a transplant after starting dialysis. Early referral occur when the agent was initiated, often with large loading also allows adequate time to identify suitable living donors; doses, and would not show calcifications in the underlying if no living donor is available, early listing is essential to vessel walls on biopsy but rather thrombosis. begin the waiting process for a deceased-donor kidney. Referral for evaluation will be appropriate if this patient selects this mode of RRT following RRT education. ¢ Calciphylaxis (calcific uremic arteriolopathy) is char- acterized by calcifications in the dermal arterioles resulting in painful ischemic skin lesions and is an e Patients with progressive chronic kidney disease and increasingly recognized complication of end-stage an estimated glomerular filtration rate <30 mL/min/ kidney disease. 1.73 m? should be referred to a renal replacement e Many patients with calciphylaxis have severe second- therapy education program. ary hyperparathyroidism and elevated calcium- phosphorous product. Bibliography Kurella Tamura M, Li S, Chen SC, et al. Educational programs improve the preparation for dialysis and survival of patients with chronic kidney Bibliography disease. Kidney Int. 2014;85:686-692. [PMID: 24067435] doi:10.1038/ Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. ki.2013.369 2018;378:1704-1714. [PMID: 29719190] doi:10.1056/NEJMra1505292 Item 47 Answer: A Item 48 Answer: C Educational Objective: Diagnosis calciphylaxis in end- Educational Objective: Diagnose fibromuscular stage kidney disease. dysplasia.

Item 47 Answer: A Item 48 Answer: C Educational Objective: Diagnosis calciphylaxis in end- Educational Objective: Diagnose fibromuscular stage kidney disease. dysplasia. The most likely diagnosis is calciphylaxis (calcific uremic arte- The most appropriate diagnostic test to perform next is renal riolopathy) (Option A). This patient with dialysis-dependent artery CT angiography (Option C). Fibromuscular dysplasia end-stage kidney disease (ESKD) has developed a painful should be considered in this young woman with new-onset ulcer on the left calf with central necrosis and a skin biopsy hypertension and an abdominal bruit. Fibromuscular dysplasia 144

__ Answers and Critiques is a noninflammatory, nonatherosclerotic form of renovascu- resistance is seen with tubulointerstitial disease, including lar disease of unknown etiology that affects medium-sized urinary obstruction, sickle cell disease, medullary cystic kid- arteries. Fibromuscular dysplasia typically occurs in young ney disease, and kidney transplant rejection. Drug-induced persons, particularly women <35 years of age. The abrupt onset type 4 RTA can be caused by numerous drugs that reduce of hypertension in a young patient with a lateralizing abdom- aldosterone production, including ACE inhibitors, angiotensin inal bruit suggests the diagnosis. For patients with suspected receptor blockers, heparin, and NSAIDs. Patients with type 4 renal artery fibromuscular dysplasia, CT angiography (CTA) RTA have a positive urine anion gap ({Urine Sodium + Urine is the initial imaging modality of choice. Contrast-enhanced Potassium] — Urine Chloride), indicating a reduced excretion magnetic resonance angiography (MRA) is an alternative when of acid in the form of ammonium and chloride but a urine pH CTA is contraindicated. Duplex ultrasound may be used as the <5.5. Hyperkalemia decreases ammonia production with con- first diagnostic procedure in specialized centers with extensive sequent lower ammonium excretion and therefore results in expertise with this imaging modality. Patients with fibromus- the positive urine anion gap. Due to the inadequate amount of cular dysplasia are at risk for aneurysm formation and/or dis- ammonia available to buffer protons, the few protons that are wn o section, most commonly of the renal, carotid, and intracranial secreted distally will result in the low urine pH (<5.5). Treat- 3

is a noninflammatory, nonatherosclerotic form of renovascu- resistance is seen with tubulointerstitial disease, including lar disease of unknown etiology that affects medium-sized urinary obstruction, sickle cell disease, medullary cystic kid- arteries. Fibromuscular dysplasia typically occurs in young ney disease, and kidney transplant rejection. Drug-induced persons, particularly women <35 years of age. The abrupt onset type 4 RTA can be caused by numerous drugs that reduce of hypertension in a young patient with a lateralizing abdom- aldosterone production, including ACE inhibitors, angiotensin inal bruit suggests the diagnosis. For patients with suspected receptor blockers, heparin, and NSAIDs. Patients with type 4 renal artery fibromuscular dysplasia, CT angiography (CTA) RTA have a positive urine anion gap ({Urine Sodium + Urine is the initial imaging modality of choice. Contrast-enhanced Potassium] — Urine Chloride), indicating a reduced excretion magnetic resonance angiography (MRA) is an alternative when of acid in the form of ammonium and chloride but a urine pH CTA is contraindicated. Duplex ultrasound may be used as the <5.5. Hyperkalemia decreases ammonia production with con- first diagnostic procedure in specialized centers with extensive sequent lower ammonium excretion and therefore results in expertise with this imaging modality. Patients with fibromus- the positive urine anion gap. Due to the inadequate amount of cular dysplasia are at risk for aneurysm formation and/or dis- ammonia available to buffer protons, the few protons that are wn o section, most commonly of the renal, carotid, and intracranial secreted distally will result in the low urine pH (<5.5). Treat- 3 arteries. Patients with fibromuscular dysplasia should undergo ment is focused on correcting the underlying cause if possible. = Nonselective B-blockers such as atenolol (Option A) a at least one-time assessment for intracranial aneurysm with oO brain CTA or MRA. block the B-2-adrenergic facilitation of potassium uptake sc = A plasma aldosterone concentration/plasma renin activ- by the cells. The increase in serum potassium is usually very } wn ity ratio (Option A) is obtained in patients with a clinical sus- modest unless B-blockade occurs in the context of a potas- os o picion for primary hyperaldosteronism; this patient does not sium load. B-Blockers do not cause a metabolic acidosis. = have hypokalemia or a metabolic alkalosis that would raise Although chronic kidney disease (Option B) may result wn = suspicion for hyperaldosteronism. Furthermore, primary in hyperkalemia and metabolic acidosis, the acidosis does =<

arteries. Patients with fibromuscular dysplasia should undergo ment is focused on correcting the underlying cause if possible. = Nonselective B-blockers such as atenolol (Option A) a at least one-time assessment for intracranial aneurysm with oO brain CTA or MRA. block the B-2-adrenergic facilitation of potassium uptake sc = A plasma aldosterone concentration/plasma renin activ- by the cells. The increase in serum potassium is usually very } wn ity ratio (Option A) is obtained in patients with a clinical sus- modest unless B-blockade occurs in the context of a potas- os o picion for primary hyperaldosteronism; this patient does not sium load. B-Blockers do not cause a metabolic acidosis. = have hypokalemia or a metabolic alkalosis that would raise Although chronic kidney disease (Option B) may result wn = suspicion for hyperaldosteronism. Furthermore, primary in hyperkalemia and metabolic acidosis, the acidosis does =< hyperaldosteronism cannot explain the abdominal bruit. not usually develop until the glomerular filtration rate (GFR) Plasma fractionated metanephrines (Option B) are is <40 mL/min/1.73 m?, and hyperkalemia is usually not obtained to screen for a pheochromocytoma. The absence present until stage G4 disease (GFR <30 mL/min/1.73 m?). of episodic palpitations, headaches, and tachycardia make Although diarrhea (Option C) may be associated with pheochromocytomaa less likely diagnosis in this patient and normal anion gap metabolic acidosis, the urine anion gap it cannot explain the abdominal bruit. would be negative; this patient has a positive urine anion gap. There is no indication to obtain a urine albumin-creati- The normal anion gap of type 1 (hypokalemic distal) nine ratio (Option D), as her urinalysis does not show blood RTA (Option D) results from a distal tubular defect and that would raise suspicion for glomerulonephritis, which associated impaired excretion of hydrogen ions by the distal would be another cause of secondary hypertension. nephron. Although the urine anion gap is generally positive, type 1 RTA is usually associated with hypokalemia and urine pH>5.5, which are not present in this patient. e Fibromuscular dysplasia typically occurs in young persons, particularly women <35 years of age, with the abrupt onset of hypertension. ¢ Diabetes mellitus is a common cause of type 4 (hyper- kalemic distal) renal tubular acidosis characterized by e Renal artery CT angiography is the most appropriate hyperkalemia, a normal anion gap metabolic acidosis, diagnostic test to evaluate for fibromuscular dysplasia. and a urine pH <5.5.

hyperaldosteronism cannot explain the abdominal bruit. not usually develop until the glomerular filtration rate (GFR) Plasma fractionated metanephrines (Option B) are is <40 mL/min/1.73 m?, and hyperkalemia is usually not obtained to screen for a pheochromocytoma. The absence present until stage G4 disease (GFR <30 mL/min/1.73 m?). of episodic palpitations, headaches, and tachycardia make Although diarrhea (Option C) may be associated with pheochromocytomaa less likely diagnosis in this patient and normal anion gap metabolic acidosis, the urine anion gap it cannot explain the abdominal bruit. would be negative; this patient has a positive urine anion gap. There is no indication to obtain a urine albumin-creati- The normal anion gap of type 1 (hypokalemic distal) nine ratio (Option D), as her urinalysis does not show blood RTA (Option D) results from a distal tubular defect and that would raise suspicion for glomerulonephritis, which associated impaired excretion of hydrogen ions by the distal would be another cause of secondary hypertension. nephron. Although the urine anion gap is generally positive, type 1 RTA is usually associated with hypokalemia and urine pH>5.5, which are not present in this patient. e Fibromuscular dysplasia typically occurs in young persons, particularly women <35 years of age, with the abrupt onset of hypertension. ¢ Diabetes mellitus is a common cause of type 4 (hyper- kalemic distal) renal tubular acidosis characterized by e Renal artery CT angiography is the most appropriate hyperkalemia, a normal anion gap metabolic acidosis, diagnostic test to evaluate for fibromuscular dysplasia. and a urine pH <5.5. Bibliography ¢ Drug-induced type 4 (hyperkalemic distal) renal Gornik HL, Persu A, Adlam D, et al. First International Consensus on the tubular acidosis can be caused by ACE inhibitors, diagnosis and management of fibromuscular dysplasia. Vasc Med. 2019; angiotensin receptor blockers, heparin, and NSAIDs. 24:164-189. [PMID: 30648921] doi:10.1177/1358863X18821816

Bibliography ¢ Drug-induced type 4 (hyperkalemic distal) renal Gornik HL, Persu A, Adlam D, et al. First International Consensus on the tubular acidosis can be caused by ACE inhibitors, diagnosis and management of fibromuscular dysplasia. Vasc Med. 2019; angiotensin receptor blockers, heparin, and NSAIDs. 24:164-189. [PMID: 30648921] doi:10.1177/1358863X18821816 Bibliography Item 49 Answer: E Yaxley J, Pirrone C. Review of the diagnostic evaluation of renal tubular acidosis. Ochsner J. 2016;16:525-530. [PMID: 27999512] Educational Objective: Diagnose type 4 (hyperkalemic distal) renal tubular acidosis. The most likely cause of this patient’s hyperkalemia is type Item 50 Answer: A 4 (hyperkalemic distal) renal tubular acidosis (RTA) (Option Educational Objective: Treat hypertension in a Black E). Type 4 RTA results from either aldosterone deficiency or patient with a calcium channel blocker. resistance. Primary adrenal insufficiency (Addison disease) or hyporeninemic hypoaldosteronism may cause aldoste- In addition to continuing therapeutic lifestyle interventions, rone deficiency. Hyporeninemic hypoaldosteronism is a more the most appropriate treatment for this Black patient is to common cause and may occur in the presence of various begin antihypertensive medication treatment with amlodi- kidney diseases, most often diabetes mellitus. Aldosterone pine (Option A), a calcium channel blocker (CCB). Lifestyle 145

Answers and Critiques _ modification (i.e., weight reduction, dietary modification, of extreme physical exertion. Inadequately conditioned indi- and increased physical activity) is particularly important in viduals who engage in extreme physical challenges under Black Americans for prevention and first-line or adjunctive conditions promoting rapid fluid loss are at risk. Rhabdomy- therapy of hypertension; however, most patients will require olysis causes acute tubular necrosis (ATN), which is believed the addition of pharmacologic therapy. For adults without to be mediated through a combination of direct toxic effects additional markers of increased cardiovascular risk, a blood of myoglobin, associated oxygen-free radical production, pressure (BP) target of <130/80 mm Hg is reasonable. Data and local renal vasoconstriction. Rhabdomyolysis-induced show that, in Black individuals, CCBs as well as thiazide ATN is more likely to occur with serum creatine kinase (CK) diuretics are more effective in lowering BP and cardiovascu- levels >5000 U/L. In addition to elevated serum CK and cre- lar events than renin-angiotensin system (RAS) inhibitors, atinine levels, hyperkalemia, hypocalcemia, hyperphospha- such as ACE inhibitors, angiotensin receptor blockers (ARBs), temia, hyperuricemia, metabolic acidosis, increased lactate and direct renin inhibitors. Therefore, initial antihypertensive dehydrogenase concentration, and increased aspartate and a= medication therapy should include a CCB or thiazide diuretic alanine aminotransferase levels can occur. Urinary findings = wn in Black patients without chronic kidney disease (CKD) or include fractional excretion of sodium <1% (caused by renal = heart failure, such as this patient. vasoconstriction), myoglobinuria, pigmented (red) granu- o = wn RAS inhibitors, such as lisinopril and losartan (Options lar casts, and a urine dipstick positive for blood with the aa B, C), are recommended in patients with hypertension, dia- absence of a significant number of erythrocytes on urine = Q. betes mellitus, nephropathy, and heart failure, or following microscopy. QO me a myocardial infarction, regardless of race or ethnicity. For Immune-mediated necrotizing myopathy (Option =. patients with CKD, initial or add-on therapy should include A) typically presents with progressive proximal weak- 2 = an ACE inhibitor or ARB, especially for those with proteinuria. ness and an elevated serum CK level; diagnosis is based o 177) There is no evidence of CKD in this patient, given the nor- on muscle biopsy findings of necrotic fibers with limited mal serum creatinine level and absence of an elevated urine inflammation. Onset can be triggered by statins, or it albumin-creatinine ratio. This patient also has no history of may present as a paraneoplastic syndrome. The onset heart failure or recent myocardial infarction that would oth- can be acute or slowly progressive but does not cause erwise be an indication for an ACE inhibitor or ARB. ATN. B-Blockers, such as metoprolol (Option D), are rec- The inflammatory myopathies (Option B) commonly ommended as initial or add-on therapy for hypertension present with symmetric proximal muscle weakness without in patients with heart failure or following a myocardial substantial muscle pain or tenderness. Serum CK is almost infarction, regardless of race or ethnicity. There is inadequate universally elevated in the inflammatory myopathies and is evidence to support the initial use of B-blockers to treat a marker of muscle damage, but the urinalysis is normal. hypertension in the absence of these specific cardiovascular The onset tends to be insidious and presence of pain or comorbidities. This patient has no history of coronary artery tenderness should prompt considerations of other causes of disease or heart failure and has no other compelling cardio- myopathy. vascular indication for treatment with metoprolol. March hemoglobinuria (Option C) develops after physical erythrocyte destruction in the soles of the feet in response to long-distance running or marching. Both hema- e In Black patients with hypertension, a calcium channel turia and hemoglobinuria due to hemolysis may result in blocker or a thiazide diuretic is the preferred initial agent. reddish-brown urine. Serum CK levels in these patients will

modification (i.e., weight reduction, dietary modification, of extreme physical exertion. Inadequately conditioned indi- and increased physical activity) is particularly important in viduals who engage in extreme physical challenges under Black Americans for prevention and first-line or adjunctive conditions promoting rapid fluid loss are at risk. Rhabdomy- therapy of hypertension; however, most patients will require olysis causes acute tubular necrosis (ATN), which is believed the addition of pharmacologic therapy. For adults without to be mediated through a combination of direct toxic effects additional markers of increased cardiovascular risk, a blood of myoglobin, associated oxygen-free radical production, pressure (BP) target of <130/80 mm Hg is reasonable. Data and local renal vasoconstriction. Rhabdomyolysis-induced show that, in Black individuals, CCBs as well as thiazide ATN is more likely to occur with serum creatine kinase (CK) diuretics are more effective in lowering BP and cardiovascu- levels >5000 U/L. In addition to elevated serum CK and cre- lar events than renin-angiotensin system (RAS) inhibitors, atinine levels, hyperkalemia, hypocalcemia, hyperphospha- such as ACE inhibitors, angiotensin receptor blockers (ARBs), temia, hyperuricemia, metabolic acidosis, increased lactate and direct renin inhibitors. Therefore, initial antihypertensive dehydrogenase concentration, and increased aspartate and a= medication therapy should include a CCB or thiazide diuretic alanine aminotransferase levels can occur. Urinary findings = wn in Black patients without chronic kidney disease (CKD) or include fractional excretion of sodium <1% (caused by renal = heart failure, such as this patient. vasoconstriction), myoglobinuria, pigmented (red) granu- o = wn RAS inhibitors, such as lisinopril and losartan (Options lar casts, and a urine dipstick positive for blood with the aa B, C), are recommended in patients with hypertension, dia- absence of a significant number of erythrocytes on urine = Q. betes mellitus, nephropathy, and heart failure, or following microscopy. QO me a myocardial infarction, regardless of race or ethnicity. For Immune-mediated necrotizing myopathy (Option =. patients with CKD, initial or add-on therapy should include A) typically presents with progressive proximal weak- 2 = an ACE inhibitor or ARB, especially for those with proteinuria. ness and an elevated serum CK level; diagnosis is based o 177) There is no evidence of CKD in this patient, given the nor- on muscle biopsy findings of necrotic fibers with limited mal serum creatinine level and absence of an elevated urine inflammation. Onset can be triggered by statins, or it albumin-creatinine ratio. This patient also has no history of may present as a paraneoplastic syndrome. The onset heart failure or recent myocardial infarction that would oth- can be acute or slowly progressive but does not cause erwise be an indication for an ACE inhibitor or ARB. ATN. B-Blockers, such as metoprolol (Option D), are rec- The inflammatory myopathies (Option B) commonly ommended as initial or add-on therapy for hypertension present with symmetric proximal muscle weakness without in patients with heart failure or following a myocardial substantial muscle pain or tenderness. Serum CK is almost infarction, regardless of race or ethnicity. There is inadequate universally elevated in the inflammatory myopathies and is evidence to support the initial use of B-blockers to treat a marker of muscle damage, but the urinalysis is normal. hypertension in the absence of these specific cardiovascular The onset tends to be insidious and presence of pain or comorbidities. This patient has no history of coronary artery tenderness should prompt considerations of other causes of disease or heart failure and has no other compelling cardio- myopathy. vascular indication for treatment with metoprolol. March hemoglobinuria (Option C) develops after physical erythrocyte destruction in the soles of the feet in response to long-distance running or marching. Both hema- e In Black patients with hypertension, a calcium channel turia and hemoglobinuria due to hemolysis may result in blocker or a thiazide diuretic is the preferred initial agent. reddish-brown urine. Serum CK levels in these patients will e §-Blockers are not indicated as first-line therapy for not be elevated.

modification (i.e., weight reduction, dietary modification, of extreme physical exertion. Inadequately conditioned indi- and increased physical activity) is particularly important in viduals who engage in extreme physical challenges under Black Americans for prevention and first-line or adjunctive conditions promoting rapid fluid loss are at risk. Rhabdomy- therapy of hypertension; however, most patients will require olysis causes acute tubular necrosis (ATN), which is believed the addition of pharmacologic therapy. For adults without to be mediated through a combination of direct toxic effects additional markers of increased cardiovascular risk, a blood of myoglobin, associated oxygen-free radical production, pressure (BP) target of <130/80 mm Hg is reasonable. Data and local renal vasoconstriction. Rhabdomyolysis-induced show that, in Black individuals, CCBs as well as thiazide ATN is more likely to occur with serum creatine kinase (CK) diuretics are more effective in lowering BP and cardiovascu- levels >5000 U/L. In addition to elevated serum CK and cre- lar events than renin-angiotensin system (RAS) inhibitors, atinine levels, hyperkalemia, hypocalcemia, hyperphospha- such as ACE inhibitors, angiotensin receptor blockers (ARBs), temia, hyperuricemia, metabolic acidosis, increased lactate and direct renin inhibitors. Therefore, initial antihypertensive dehydrogenase concentration, and increased aspartate and a= medication therapy should include a CCB or thiazide diuretic alanine aminotransferase levels can occur. Urinary findings = wn in Black patients without chronic kidney disease (CKD) or include fractional excretion of sodium <1% (caused by renal = heart failure, such as this patient. vasoconstriction), myoglobinuria, pigmented (red) granu- o = wn RAS inhibitors, such as lisinopril and losartan (Options lar casts, and a urine dipstick positive for blood with the aa B, C), are recommended in patients with hypertension, dia- absence of a significant number of erythrocytes on urine = Q. betes mellitus, nephropathy, and heart failure, or following microscopy. QO me a myocardial infarction, regardless of race or ethnicity. For Immune-mediated necrotizing myopathy (Option =. patients with CKD, initial or add-on therapy should include A) typically presents with progressive proximal weak- 2 = an ACE inhibitor or ARB, especially for those with proteinuria. ness and an elevated serum CK level; diagnosis is based o 177) There is no evidence of CKD in this patient, given the nor- on muscle biopsy findings of necrotic fibers with limited mal serum creatinine level and absence of an elevated urine inflammation. Onset can be triggered by statins, or it albumin-creatinine ratio. This patient also has no history of may present as a paraneoplastic syndrome. The onset heart failure or recent myocardial infarction that would oth- can be acute or slowly progressive but does not cause erwise be an indication for an ACE inhibitor or ARB. ATN. B-Blockers, such as metoprolol (Option D), are rec- The inflammatory myopathies (Option B) commonly ommended as initial or add-on therapy for hypertension present with symmetric proximal muscle weakness without in patients with heart failure or following a myocardial substantial muscle pain or tenderness. Serum CK is almost infarction, regardless of race or ethnicity. There is inadequate universally elevated in the inflammatory myopathies and is evidence to support the initial use of B-blockers to treat a marker of muscle damage, but the urinalysis is normal. hypertension in the absence of these specific cardiovascular The onset tends to be insidious and presence of pain or comorbidities. This patient has no history of coronary artery tenderness should prompt considerations of other causes of disease or heart failure and has no other compelling cardio- myopathy. vascular indication for treatment with metoprolol. March hemoglobinuria (Option C) develops after physical erythrocyte destruction in the soles of the feet in response to long-distance running or marching. Both hema- e In Black patients with hypertension, a calcium channel turia and hemoglobinuria due to hemolysis may result in blocker or a thiazide diuretic is the preferred initial agent. reddish-brown urine. Serum CK levels in these patients will e §-Blockers are not indicated as first-line therapy for not be elevated. hypertension in the absence of a compelling reason such as heart failure or recent myocardial infarction, ¢ Rhabdomyolysis is associated with elevated serum regardless of race or ethnicity. creatinine and creatine kinase levels and may be associated with hyperkalemia, hypocalcemia, Bibliography hyperphosphatemia, hyperuricemia, increased lac- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detec- tate dehydrogenase concentration, and metabolic tion, evaluation, and management of high blood pressure in adults: execu- acidosis. tive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. e In patients with acute tubular necrosis caused by rhab- 2018;71:1269-1324. [PMID: 29133354] doi:10.1161/HYP.0000000000000066 domyolysis, urinary sediment is characterized by amor- phous tubular debris, including heavily pigmented Item 51 Answer: D granular casts.

hypertension in the absence of a compelling reason such as heart failure or recent myocardial infarction, ¢ Rhabdomyolysis is associated with elevated serum regardless of race or ethnicity. creatinine and creatine kinase levels and may be associated with hyperkalemia, hypocalcemia, Bibliography hyperphosphatemia, hyperuricemia, increased lac- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detec- tate dehydrogenase concentration, and metabolic tion, evaluation, and management of high blood pressure in adults: execu- acidosis. tive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. e In patients with acute tubular necrosis caused by rhab- 2018;71:1269-1324. [PMID: 29133354] doi:10.1161/HYP.0000000000000066 domyolysis, urinary sediment is characterized by amor- phous tubular debris, including heavily pigmented Item 51 Answer: D granular casts. Educational Objective: Diagnose acute tubular necrosis due to rhabdomyolysis. Bibliography Chavez LO, Leon M, Einav S, et al. Beyond muscle destruction: a systematic The most likely cause of this patient’s findings is rhabdomy- review of rhabdomyolysis for clinical practice. Crit Care. 2016;20:135. olysis (Option D) caused by acute muscle injury in the setting [PMID: 27301374] doi:10.1186/s13054-016-1314-5

Educational Objective: Diagnose acute tubular necrosis due to rhabdomyolysis. Bibliography Chavez LO, Leon M, Einav S, et al. Beyond muscle destruction: a systematic The most likely cause of this patient’s findings is rhabdomy- review of rhabdomyolysis for clinical practice. Crit Care. 2016;20:135. olysis (Option D) caused by acute muscle injury in the setting [PMID: 27301374] doi:10.1186/s13054-016-1314-5 146

Answers and Critiques Item 52 Answer: B Item 53 Answer: A Educational Objective: Treat stage 1 hypertension with Educational Objective: Manage chronic hypertension nonpharmacologic and pharmacologic therapy. before conception.

Item 52 Answer: B Item 53 Answer: A Educational Objective: Treat stage 1 hypertension with Educational Objective: Manage chronic hypertension nonpharmacologic and pharmacologic therapy. before conception. The most appropriate additional management is to start The most appropriate management is to discontinue the ACE amlodipine (Option B). Adults with stage 1 hypertension (sys- inhibitor ramipril (Option A) in this patient who is planning tolic blood pressure [SBP] of 130-139 mm Hg or diastolic blood pregnancy. Renin-angiotensin system blocking agents, such pressure [DBP] of 80-89 mm Hg) who have an estimated as ACE inhibitors, angiotensin receptor blockers (ARBs), and 10-year atherosclerotic cardiovascular disease (ASCVD) event direct renin inhibitors, are contraindicated in pregnancy and risk of 210% should be managed initially with a combination should be discontinued before conception. Exposure during of nonpharmacologic and antihypertensive drug therapy and the second and third trimesters of pregnancy has been asso- have a repeat BP evaluation in 1 month. Initial pharmacologic ciated with neonatal kidney failure and death. therapy for Black patients in the absence of heart failure or In pregnant patients with chronic hypertension, the wn chronic kidney disease is either a calcium channel blocker o 2019 American College of Obstetricians and Gynecologists = (CCB), such as amlodipine, or a thiazide diuretic. (ACOG) guidelines recommend a systolic blood pressure ALS Adults with an elevated BP (SBP of 120-129 mm Hg during pregnancy of 120 to <160 mm Hg and a diastolic = (s) and a DBP <80 mm Hg) or stage 1 hypertension who have pressure of 80 to <110 mm Hg. In the setting of comorbid- =| an estimated 10-year ASCVD risk <10% should be managed ities or underlying impaired kidney function, treating at = cs with nonpharmacologic therapy and have a repeat BP eval- lower blood pressure thresholds may be appropriate. This 2 uation within 3 to 6 months (Option A). Lifestyle modifi- patient’s blood pressure is well within this range on treat- oe

The most appropriate additional management is to start The most appropriate management is to discontinue the ACE amlodipine (Option B). Adults with stage 1 hypertension (sys- inhibitor ramipril (Option A) in this patient who is planning tolic blood pressure [SBP] of 130-139 mm Hg or diastolic blood pregnancy. Renin-angiotensin system blocking agents, such pressure [DBP] of 80-89 mm Hg) who have an estimated as ACE inhibitors, angiotensin receptor blockers (ARBs), and 10-year atherosclerotic cardiovascular disease (ASCVD) event direct renin inhibitors, are contraindicated in pregnancy and risk of 210% should be managed initially with a combination should be discontinued before conception. Exposure during of nonpharmacologic and antihypertensive drug therapy and the second and third trimesters of pregnancy has been asso- have a repeat BP evaluation in 1 month. Initial pharmacologic ciated with neonatal kidney failure and death. therapy for Black patients in the absence of heart failure or In pregnant patients with chronic hypertension, the wn chronic kidney disease is either a calcium channel blocker o 2019 American College of Obstetricians and Gynecologists = (CCB), such as amlodipine, or a thiazide diuretic. (ACOG) guidelines recommend a systolic blood pressure ALS Adults with an elevated BP (SBP of 120-129 mm Hg during pregnancy of 120 to <160 mm Hg and a diastolic = (s) and a DBP <80 mm Hg) or stage 1 hypertension who have pressure of 80 to <110 mm Hg. In the setting of comorbid- =| an estimated 10-year ASCVD risk <10% should be managed ities or underlying impaired kidney function, treating at = cs with nonpharmacologic therapy and have a repeat BP eval- lower blood pressure thresholds may be appropriate. This 2 uation within 3 to 6 months (Option A). Lifestyle modifi- patient’s blood pressure is well within this range on treat- oe cations (weight loss, heart-healthy diet, sodium reduction, = ment, and her blood pressure would be expected to decline wn < potassium supplementation, increased physical activity) and during pregnancy. Therefore, monitoring her blood pres- P=

cations (weight loss, heart-healthy diet, sodium reduction, = ment, and her blood pressure would be expected to decline wn < potassium supplementation, increased physical activity) and during pregnancy. Therefore, monitoring her blood pres- P= management of cardiovascular risk factors (tobacco use, sure after discontinuation of ramipril without the initia- diabetes mellitus, hyperlipidemia) should be addressed in all tion of a replacement drug is a reasonable approach. If her patients with hypertension. This patient is at increased risk blood pressure increases beyond the target range during for an ASCVD event, and treatment with both nonpharma- pregnancy, initiation of a drug that is safe in pregnancy cologic and pharmacologic therapy is indicated. is recommended. In that event, first-line therapy includes Combination therapy with two-first line drugs (Option methyldopa, labetalol, and nifedipine. C) (with the exception of an ACE inhibitor and ARB com- Pregnant patients with acute and severe hypertension bination) that act by different mechanisms is indicated for have been successfully and safely treated with parenteral patients with stage 2 hypertension (>140/90 mm Hg). Com- hydralazine. There is less experience in its use as a routine bined pharmacologic therapy is not indicated in this patient oral antihypertensive drug in pregnant women with chronic with stage 1 hypertension. hypertension. Hydralazine is an unlikely first-line drug ACE inhibitors such as lisinopril (Option D), angio- (Option B) for pregnant women needing antihypertensive tensin receptor blockers (ARBs) such as losartan, thiazide treatment because it causes reflex tachycardia, often neces- diuretics such as chlorthalidone, and CCBs are all first- sitating combination with a B-blocking drug, and results in line antihypertensive medication classes. However, in the fluid retention, often requiring the addition of a diuretic. absence of heart failure or chronic kidney disease, CCBs or Mineralocorticoid receptor antagonists such as spirono- thiazide diuretics are preferred in Black patients because lactone (Option C) and eplerenone also block the renin- they are the most efficacious. angiotensin system. This class of drug is often used in patients with hyperaldosteronism and resistant hypertension, but it has not been shown to be safe in pregnancy. e Adults with stage 1 hypertension who have an esti- Not discontinuing the ramipril (Option D) in this mated 10-year atherosclerotic cardiovascular disease patient at this point in time is unsafe. The safest approach is event risk of <10% should be managed initially with to discontinue any inhibitor of the renin-angiotensin system nonpharmacologic therapy. before conception. e Adults with stage 1 hypertension who have an esti- mated 10-year atherosclerotic cardiovascular disease event risk of [10% should be managed initially with e Renin-angiotensin system blocking agents (ACE nonpharmacologic and antihypertensive drug therapy. inhibitors, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor antago- nists) are contraindicated in pregnancy and should be Bibliography discontinued before conception. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, ¢ Chronic hypertension guidelines for pregnant women detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart recommenda systolic blood pressure of 120 to <160 mm Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Hg and a diastolic pressure of 80 to <110 mm Hg. 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016 /j.jacc.2017.11.006

management of cardiovascular risk factors (tobacco use, sure after discontinuation of ramipril without the initia- diabetes mellitus, hyperlipidemia) should be addressed in all tion of a replacement drug is a reasonable approach. If her patients with hypertension. This patient is at increased risk blood pressure increases beyond the target range during for an ASCVD event, and treatment with both nonpharma- pregnancy, initiation of a drug that is safe in pregnancy cologic and pharmacologic therapy is indicated. is recommended. In that event, first-line therapy includes Combination therapy with two-first line drugs (Option methyldopa, labetalol, and nifedipine. C) (with the exception of an ACE inhibitor and ARB com- Pregnant patients with acute and severe hypertension bination) that act by different mechanisms is indicated for have been successfully and safely treated with parenteral patients with stage 2 hypertension (>140/90 mm Hg). Com- hydralazine. There is less experience in its use as a routine bined pharmacologic therapy is not indicated in this patient oral antihypertensive drug in pregnant women with chronic with stage 1 hypertension. hypertension. Hydralazine is an unlikely first-line drug ACE inhibitors such as lisinopril (Option D), angio- (Option B) for pregnant women needing antihypertensive tensin receptor blockers (ARBs) such as losartan, thiazide treatment because it causes reflex tachycardia, often neces- diuretics such as chlorthalidone, and CCBs are all first- sitating combination with a B-blocking drug, and results in line antihypertensive medication classes. However, in the fluid retention, often requiring the addition of a diuretic. absence of heart failure or chronic kidney disease, CCBs or Mineralocorticoid receptor antagonists such as spirono- thiazide diuretics are preferred in Black patients because lactone (Option C) and eplerenone also block the renin- they are the most efficacious. angiotensin system. This class of drug is often used in patients with hyperaldosteronism and resistant hypertension, but it has not been shown to be safe in pregnancy. e Adults with stage 1 hypertension who have an esti- Not discontinuing the ramipril (Option D) in this mated 10-year atherosclerotic cardiovascular disease patient at this point in time is unsafe. The safest approach is event risk of <10% should be managed initially with to discontinue any inhibitor of the renin-angiotensin system nonpharmacologic therapy. before conception. e Adults with stage 1 hypertension who have an esti- mated 10-year atherosclerotic cardiovascular disease event risk of [10% should be managed initially with e Renin-angiotensin system blocking agents (ACE nonpharmacologic and antihypertensive drug therapy. inhibitors, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor antago- nists) are contraindicated in pregnancy and should be Bibliography discontinued before conception. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, ¢ Chronic hypertension guidelines for pregnant women detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart recommenda systolic blood pressure of 120 to <160 mm Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Hg and a diastolic pressure of 80 to <110 mm Hg. 2018;71:e127-e248. [PMID: 29146535] doi: 10.1016 /j.jacc.2017.11.006 147

Answers and Critiques Bibliography cobicistat, dolutegravir, and bictegravir) reduce proximal ACOG practice bulletin no. 203: chronic hypertension in pregnancy. tubule secretion of creatinine, resulting in increases in serum Obstet Gynecol. 2019;133:e26-e50. [PMID: 30575676] doi:10.1097/ creatinine that are nonprogressive; they do not affect glomer- AOG.0000000000003020 ular filtration rate (GFR). This patient’s antiretroviral regimen was changed to include dolutegravir 6 weeks earlier. Slight

Bibliography cobicistat, dolutegravir, and bictegravir) reduce proximal ACOG practice bulletin no. 203: chronic hypertension in pregnancy. tubule secretion of creatinine, resulting in increases in serum Obstet Gynecol. 2019;133:e26-e50. [PMID: 30575676] doi:10.1097/ creatinine that are nonprogressive; they do not affect glomer- AOG.0000000000003020 ular filtration rate (GFR). This patient’s antiretroviral regimen was changed to include dolutegravir 6 weeks earlier. Slight Item 54 Answer: C increases in serum creatinine of 0.2 mg/dL to 0.3 mg/dL (17.7- 26.5 umol/L) may occur. This is more pronounced in patients Educational Objective: Treat uric acid kidney stones. with chronic kidney disease (CKD), in which creatinine secre- The most appropriate treatment is potassium citrate (Option tion contributes proportionately more to creatinine clearance. C). Acute management of symptomatic nephrolithiasis is In patients with CKD who are taking the integrase inhibi- aimed at pain management and facilitation of stone passage. tors dolutegravir or bictegravir, the non-nucleoside reverse Pain can be relieved by NSAIDs and opioids as needed. Stone transcriptase inhibitor rilpivirine, or the pharmacokinetic > passage decreases with increasing size. Only 50% of stones enhancer (CYP3A inhibitor) cobicistat, serum creatinine ele- = n” >6 mm will pass, and stones >10 mm are extremely unlikely to vations are nonprogressive and will remain stable within 1 to = pass spontaneously. This patient most likely has a uric acid kid- 2 weeks of initiation. Therefore, in the absence of other signs of i) = wn ney stone. On helical CT scan, the density of the stone, as mea- kidney disease (hematuria, pyuria, or increasing proteinuria), ro) = sured by Hounsfield units, is suggestive of uric acid. Patients and with a serum creatinine that has remained unchanged Q. with a uric acid kidney stone will have an acidic urine pH, as since the patient’s 4-week assessment, no further evaluation is a = seen in this patient (pH 5.0). Uric acid stones are also more necessary. In this case, measuring the patient’s serum cystatin =. common in individuals with metabolic syndrome, as seen in C level could be a helpful confirmatory test, because the level 2 = this patient. The most effective treatment for uric acid stones is is not affected by these medications. @ wn to alkalinize the urine, as uric acid is readily soluble in alkaline Discontinuation of combined lisinopril-hydrochloro- urine. If the urine pH is increased to 6.5 to 7.0, more than 90% thiazide (Option A) is not necessary. This patient has been of uric acid will be converted to soluble urate salts, dissolving taking her current antihypertensive combination for 6 years, the stone. Administration of potassium citrate at a dose of 40 and it is unlikely to have caused this acute increase in serum to 80 mEq/d will effectively alkalinize the urine and reduce the creatinine; the hemodynamic effects of ACE inhibitors on size of the stone, allowing it to rapidly transit to the bladder. glomerular filtration occur within days of initiation. Allopurinol (Option A) should be reserved to treat A 24-hour urine creatinine clearance (Option B) will patients with gout and/or recurrent uric acid kidney stones be decreased in this case (due to drug-related lower creat- that are unresponsive to alkalinization and increased fluid inine secretion) and will not provide additional diagnostic intake, neither of which applies to this patient. information. Lithotripsy (Option B) is an appropriate treatment for Returning to the prior antiretroviral regimen (Option C) kidney stones >6 mm that are unlikely to pass. However, for is not indicated, as the effects of dolutegravir on the patient’s this patient, the 5-mm stone will likely pass, especially if the serum creatinine level does not indicate GFR decline. urine pH is increased to 6.5 to 7.0. The data concerning the use of tamsulosin (Option D) to facilitate stone passage are controversial. But because there ¢ Some medications (such as cimetidine, trimethoprim, are few adverse effects attributed to this medication, many cobicistat, dolutegravir, and bictegravir) reduce proxi- experts recommend its use. In the case of uric acid stones, mal tubule secretion of creatinine, resulting in urinary alkalinization with the use of potassium citrate is a increases in serum creatinine. more effective treatment. Bibliography Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral drugs. e The most effective treatment to facilitate the passage Nephrol Dial Transplant. 2017;32:434-439. [PMID: 27190354] doi:10.1093/ ndt/gfw064 of uric acid stones is urinary alkalinization with potassium citrate.

Item 54 Answer: C increases in serum creatinine of 0.2 mg/dL to 0.3 mg/dL (17.7- 26.5 umol/L) may occur. This is more pronounced in patients Educational Objective: Treat uric acid kidney stones. with chronic kidney disease (CKD), in which creatinine secre- The most appropriate treatment is potassium citrate (Option tion contributes proportionately more to creatinine clearance. C). Acute management of symptomatic nephrolithiasis is In patients with CKD who are taking the integrase inhibi- aimed at pain management and facilitation of stone passage. tors dolutegravir or bictegravir, the non-nucleoside reverse Pain can be relieved by NSAIDs and opioids as needed. Stone transcriptase inhibitor rilpivirine, or the pharmacokinetic > passage decreases with increasing size. Only 50% of stones enhancer (CYP3A inhibitor) cobicistat, serum creatinine ele- = n” >6 mm will pass, and stones >10 mm are extremely unlikely to vations are nonprogressive and will remain stable within 1 to = pass spontaneously. This patient most likely has a uric acid kid- 2 weeks of initiation. Therefore, in the absence of other signs of i) = wn ney stone. On helical CT scan, the density of the stone, as mea- kidney disease (hematuria, pyuria, or increasing proteinuria), ro) = sured by Hounsfield units, is suggestive of uric acid. Patients and with a serum creatinine that has remained unchanged Q. with a uric acid kidney stone will have an acidic urine pH, as since the patient’s 4-week assessment, no further evaluation is a = seen in this patient (pH 5.0). Uric acid stones are also more necessary. In this case, measuring the patient’s serum cystatin =. common in individuals with metabolic syndrome, as seen in C level could be a helpful confirmatory test, because the level 2 = this patient. The most effective treatment for uric acid stones is is not affected by these medications. @ wn to alkalinize the urine, as uric acid is readily soluble in alkaline Discontinuation of combined lisinopril-hydrochloro- urine. If the urine pH is increased to 6.5 to 7.0, more than 90% thiazide (Option A) is not necessary. This patient has been of uric acid will be converted to soluble urate salts, dissolving taking her current antihypertensive combination for 6 years, the stone. Administration of potassium citrate at a dose of 40 and it is unlikely to have caused this acute increase in serum to 80 mEq/d will effectively alkalinize the urine and reduce the creatinine; the hemodynamic effects of ACE inhibitors on size of the stone, allowing it to rapidly transit to the bladder. glomerular filtration occur within days of initiation. Allopurinol (Option A) should be reserved to treat A 24-hour urine creatinine clearance (Option B) will patients with gout and/or recurrent uric acid kidney stones be decreased in this case (due to drug-related lower creat- that are unresponsive to alkalinization and increased fluid inine secretion) and will not provide additional diagnostic intake, neither of which applies to this patient. information. Lithotripsy (Option B) is an appropriate treatment for Returning to the prior antiretroviral regimen (Option C) kidney stones >6 mm that are unlikely to pass. However, for is not indicated, as the effects of dolutegravir on the patient’s this patient, the 5-mm stone will likely pass, especially if the serum creatinine level does not indicate GFR decline. urine pH is increased to 6.5 to 7.0. The data concerning the use of tamsulosin (Option D) to facilitate stone passage are controversial. But because there ¢ Some medications (such as cimetidine, trimethoprim, are few adverse effects attributed to this medication, many cobicistat, dolutegravir, and bictegravir) reduce proxi- experts recommend its use. In the case of uric acid stones, mal tubule secretion of creatinine, resulting in urinary alkalinization with the use of potassium citrate is a increases in serum creatinine. more effective treatment. Bibliography Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral drugs. e The most effective treatment to facilitate the passage Nephrol Dial Transplant. 2017;32:434-439. [PMID: 27190354] doi:10.1093/ ndt/gfw064 of uric acid stones is urinary alkalinization with potassium citrate. Item 56 Answer: A Bibliography Heilberg IP. Treatment of patients with uric acid stones. Urolithiasis. Educational Objective: Treat difficult-to-control hyper- 2016;44:57-63. [PMID: 26645868] doi:10.1007/s00240-015-0843-8 tension by adding a diuretic.

Item 56 Answer: A Bibliography Heilberg IP. Treatment of patients with uric acid stones. Urolithiasis. Educational Objective: Treat difficult-to-control hyper- 2016;44:57-63. [PMID: 26645868] doi:10.1007/s00240-015-0843-8 tension by adding a diuretic. The most appropriate next step in management is to add Item 55 Answer: D chlorthalidone, a thiazide diuretic (Option A). Resistant hypertension is defined as blood pressure (BP) that remains Educational Objective: Identify drugs as a nonglomerular above goal despite concurrent use of three antihypertensive cause of an increase in serum creatinine level. agents of different classes, or BP at goal but requiring four No further management (Option D) is indicated for this or more medications. One of these medications must be a patient. Some medications (such as cimetidine, trimethoprim, diuretic. Suboptimal antihypertensive therapy in patients 148

Answers and Critiques with difficult-to-control hypertension is frequently the result osmolality is elevated (560 mOsm/kg H,0), likely indicating of not including a diuretic agent, which ensures that extra- a solute diuresis. This can be further categorized as an elec- cellular volume expansion is prevented or treated. Therefore, trolyte diuresis or a nonelectrolyte diuresis. Because the total before a diagnosis of resistant hypertension is made or eval- electrolyte in her urine comprises <50% of the urine osmolal- uation is initiated for secondary causes of hypertension, the ity [2 x (Urine Sodium + Urine Potassium)], this patient is hav- patient should be treated with an appropriate diuretic medi- ing a solute diuresis. She takes dexamethasone, which, due cation, with attention to effective dose and dosing frequency. to its catabolic effect, has increased the blood urea nitrogen, Although hydrochlorothiazide is the most commonly used resulting in a urea diuresis with subsequent loss of water. This thiazide diuretic, chlorthalidone has a longer half-life, which can be confirmed by measuring the urine urea concentration. allows once-daily dosing; some evidence from trials suggests Treatment for this patient would be to either increase her efficacy in reducing cardiovascular events. water intake or decrease the dexamethasone dose. Obtaining a plasma aldosterone concentration/plasma Although diabetes insipidus (Option A) may occur in renin activity ratio (Option B) is not indicated at this time, patients who have undergone neurosurgery, this patient’s ”n a as there is no clinical suspicion for primary hyperaldostero- increased urine osmolality is inconsistent with diabetes =]

with difficult-to-control hypertension is frequently the result osmolality is elevated (560 mOsm/kg H,0), likely indicating of not including a diuretic agent, which ensures that extra- a solute diuresis. This can be further categorized as an elec- cellular volume expansion is prevented or treated. Therefore, trolyte diuresis or a nonelectrolyte diuresis. Because the total before a diagnosis of resistant hypertension is made or eval- electrolyte in her urine comprises <50% of the urine osmolal- uation is initiated for secondary causes of hypertension, the ity [2 x (Urine Sodium + Urine Potassium)], this patient is hav- patient should be treated with an appropriate diuretic medi- ing a solute diuresis. She takes dexamethasone, which, due cation, with attention to effective dose and dosing frequency. to its catabolic effect, has increased the blood urea nitrogen, Although hydrochlorothiazide is the most commonly used resulting in a urea diuresis with subsequent loss of water. This thiazide diuretic, chlorthalidone has a longer half-life, which can be confirmed by measuring the urine urea concentration. allows once-daily dosing; some evidence from trials suggests Treatment for this patient would be to either increase her efficacy in reducing cardiovascular events. water intake or decrease the dexamethasone dose. Obtaining a plasma aldosterone concentration/plasma Although diabetes insipidus (Option A) may occur in renin activity ratio (Option B) is not indicated at this time, patients who have undergone neurosurgery, this patient’s ”n a as there is no clinical suspicion for primary hyperaldostero- increased urine osmolality is inconsistent with diabetes =] nism such as resistant hypertension, hypokalemia, inciden- insipidus. = An electrolyte diuresis (Option B) is typically caused by .= tally discovered adrenal mass, family history of early-onset rs) hypertension, or stroke at age <40 years. This patient does intravenous administration of a large volume of 0.9% saline sc <= not have hypokalemia or a metabolic alkalosis to raise suspi- or after relief of bilateral urinary tract obstruction, result- c wv cion for hyperaldosteronism. ing in polyuria. When urine output increases, a common om o Testing for plasma fractionated metanephrines (Option response is to increase the intravenous infusion rate, which = wn C), which screens for a pheochromocytoma, is not indi- further increases the sodium load and promotes urine out- = cated. The following characteristics raise clinical suspicion put and causes an unending spiral; in this case, the urine =

nism such as resistant hypertension, hypokalemia, inciden- insipidus. = An electrolyte diuresis (Option B) is typically caused by .= tally discovered adrenal mass, family history of early-onset rs) hypertension, or stroke at age <40 years. This patient does intravenous administration of a large volume of 0.9% saline sc <= not have hypokalemia or a metabolic alkalosis to raise suspi- or after relief of bilateral urinary tract obstruction, result- c wv cion for hyperaldosteronism. ing in polyuria. When urine output increases, a common om o Testing for plasma fractionated metanephrines (Option response is to increase the intravenous infusion rate, which = wn C), which screens for a pheochromocytoma, is not indi- further increases the sodium load and promotes urine out- = cated. The following characteristics raise clinical suspicion put and causes an unending spiral; in this case, the urine = for pheochromocytoma: resistant hypertension; new-onset electrolyte concentration cannot explain the ongoing diure- hypertension or onset at a young age; paroxysmal hyperten- sis. In addition, although an increase in sodium intake will sion; episodic tachycardia, headaches, and sweating; history cause polyuria, unless the sodium load is hypertonic, it will of familial syndromes; adrenal adenoma found inciden- not result in hypernatremia. tally on imaging with or without hypertension; or pres- Dexamethasone can increase serum glucose levels. sor response during invasive procedures or anesthesia. The Although this patient’s serum glucose level is elevated, it patient has none of these indications for testing. is below the renal threshold (approximately 180 mg/dL Obtaining renal artery imaging (Option D) is not indi- {10 mmol/L]) for complete reabsorption. Therefore, a glucose cated, as there is no clinical suspicion for renal artery ste- diuresis (Option C) is not responsible for either the patient’s nosis, which includes the onset of severe hypertension in polyuria or hypernatremia. patients >55 years of age, recurrent flash pulmonary edema, refractory heart failure, or acute kidney injury after initi- ation of an ACE inhibitor or angiotensin receptor blocker. ¢ Polyuria is caused by either a water diuresis (dilute urine) or a solute diuresis (urine osmolality, 300-600 mOsm/kg H,0). e Resistant hypertension is blood pressure that remains e Polyuria caused by an osmotic diuresis is caused by above goal despite concurrent use of three antihyper- either an electrolyte diuresis or a nonelectrolyte diu- tensive agents of different classes, or blood pressure at resis (e.g., urea, glucose). goal but requiring four or more medications; one of these medications must be a diuretic. Bibliography Lindner G, Schwarz C, Funk GC. Osmotic diuresis due to urea as the cause Bibliography of hypernatraemia in critically ill patients. Nephrol Dial Transplant. 2012;27:962-967. [PMID: 21810766] doi:10.1093/ndt/gfr428 Braam B, Taler SJ, Rahman M, et al. Recognition and management of resist- ant hypertension. Clin J Am Soc Nephrol. 2017;12:524-535. [PMID: 27895136] doi:10.2215/CJN.06180616 Item 58 Answer: D Educational Objective: Evaluate a kidney transplant Item 57 Answer: D recipient for side effects of immunosuppressive therapy. Educational Objective: Identify urea diuresis as the Tacrolimus (Option D) is the most likely medication responsi- cause of hypernatremia. ble for this patient’s tremor. Immunosuppressive medications The most likely cause of this patient’s hypernatremia is urea allow successful kidney transplantation but have numer- diuresis (Option D). This patient has polyuria, which can be ous side effects that should be considered when patients on categorized as a water diuresis or a solute diuresis based on the these medications present with new symptoms. Long-term urine osmolality. In osmotic diuresis, urine osmolality is usu- maintenance therapy for most kidney transplant recipients ally between 300 and 600 mOsm/kg H,O. This patent’s urine includes a combination of calcineurin inhibitors (tacrolimus

for pheochromocytoma: resistant hypertension; new-onset electrolyte concentration cannot explain the ongoing diure- hypertension or onset at a young age; paroxysmal hyperten- sis. In addition, although an increase in sodium intake will sion; episodic tachycardia, headaches, and sweating; history cause polyuria, unless the sodium load is hypertonic, it will of familial syndromes; adrenal adenoma found inciden- not result in hypernatremia. tally on imaging with or without hypertension; or pres- Dexamethasone can increase serum glucose levels. sor response during invasive procedures or anesthesia. The Although this patient’s serum glucose level is elevated, it patient has none of these indications for testing. is below the renal threshold (approximately 180 mg/dL Obtaining renal artery imaging (Option D) is not indi- {10 mmol/L]) for complete reabsorption. Therefore, a glucose cated, as there is no clinical suspicion for renal artery ste- diuresis (Option C) is not responsible for either the patient’s nosis, which includes the onset of severe hypertension in polyuria or hypernatremia. patients >55 years of age, recurrent flash pulmonary edema, refractory heart failure, or acute kidney injury after initi- ation of an ACE inhibitor or angiotensin receptor blocker. ¢ Polyuria is caused by either a water diuresis (dilute urine) or a solute diuresis (urine osmolality, 300-600 mOsm/kg H,0). e Resistant hypertension is blood pressure that remains e Polyuria caused by an osmotic diuresis is caused by above goal despite concurrent use of three antihyper- either an electrolyte diuresis or a nonelectrolyte diu- tensive agents of different classes, or blood pressure at resis (e.g., urea, glucose). goal but requiring four or more medications; one of these medications must be a diuretic. Bibliography Lindner G, Schwarz C, Funk GC. Osmotic diuresis due to urea as the cause Bibliography of hypernatraemia in critically ill patients. Nephrol Dial Transplant. 2012;27:962-967. [PMID: 21810766] doi:10.1093/ndt/gfr428 Braam B, Taler SJ, Rahman M, et al. Recognition and management of resist- ant hypertension. Clin J Am Soc Nephrol. 2017;12:524-535. [PMID: 27895136] doi:10.2215/CJN.06180616 Item 58 Answer: D Educational Objective: Evaluate a kidney transplant Item 57 Answer: D recipient for side effects of immunosuppressive therapy. Educational Objective: Identify urea diuresis as the Tacrolimus (Option D) is the most likely medication responsi- cause of hypernatremia. ble for this patient’s tremor. Immunosuppressive medications The most likely cause of this patient’s hypernatremia is urea allow successful kidney transplantation but have numer- diuresis (Option D). This patient has polyuria, which can be ous side effects that should be considered when patients on categorized as a water diuresis or a solute diuresis based on the these medications present with new symptoms. Long-term urine osmolality. In osmotic diuresis, urine osmolality is usu- maintenance therapy for most kidney transplant recipients ally between 300 and 600 mOsm/kg H,O. This patent’s urine includes a combination of calcineurin inhibitors (tacrolimus 149

Answers and Critiques or cyclosporine), antimetabolites (mycophenolate mofetil or a capillary leak in the setting of sepsis and massive fluid azathioprine), and glucocorticoids. Tremor is an oscillatory resuscitation. The diagnosis of ACS can be confirmed through movement of a body part that is classified based on its pres- measurement of bladder pressure using an indwelling cathe- ence at rest or with action. Tremor is a side effect of cal- ter as a surrogate for intra-abdominal pressure measurement. cineurin inhibitors and is most common with tacrolimus. Appropriate treatment includes surgical decompression of the Calcineurin-induced tremor is bilateral and may affect the abdominal compartment. hands and feet. Tacrolimus tremor is activated by action, but CT urography (Option B) is the diagnostic test of choice in about 50% of cases the tremor can be classified as both for patients with unexplained hematuria and allows char- an action and resting tremor. The tremor is associated with acterization of kidney tumors and cysts. MRI with contrast elevated drug levels and may be most pronounced when drug is an alternative for evaluation of kidney masses and cysts levels peak following a dose. This patient’s tacrolimus trough when CT cannot be performed. These imaging tests would measurement should be checked, as treatment interventions not be useful in this patient with acute kidney injury. > include dose reduction if permissible, conversion to long- Indications for kidney biopsy (Option C) include glo- = 7) acting formulations, addition of a §-blocker, or conversion merular hematuria, severely increased albuminuria, acute = to an alternate agent if the tremor is debilitating and unre- or chronic kidney disease of unclear cause (in the absence oO = 7.) sponsive to other interventions. These adjustments should of atrophic kidneys), and kidney transplant dysfunction or oy be made in conjunction with the patient’s nephrologist or monitoring. Bladder pressure measurement is indicated as = Qo. transplant program. Other side effects of calcineurin inhib- the next test because it is the most likely to provide a diag- (2) = itors include new-onset type 2 diabetes mellitus, decreased nosis, obviating the need for additional testing. re glomerular filtration rate, hypertension, dyslipidemia, and Kidney ultrasonography (Option D) is helpful to s) = gingival hyperplasia. exclude obstruction, but new bilateral ureteral obstruction @ wn Metoprolol (Option A) is not causing, and may be useful is not strongly suspected in this patient and the placement in treating, this patient’s tacrolimus-related tremor. of a bladder catheter rules out acute urethral obstruction. Side effects of mycophenolate mofetil (Option B) include nausea, vomiting, diarrhea, leukopenia, and ane- mia, but not tremor. e Abdominal compartment syndrome is defined as a

or cyclosporine), antimetabolites (mycophenolate mofetil or a capillary leak in the setting of sepsis and massive fluid azathioprine), and glucocorticoids. Tremor is an oscillatory resuscitation. The diagnosis of ACS can be confirmed through movement of a body part that is classified based on its pres- measurement of bladder pressure using an indwelling cathe- ence at rest or with action. Tremor is a side effect of cal- ter as a surrogate for intra-abdominal pressure measurement. cineurin inhibitors and is most common with tacrolimus. Appropriate treatment includes surgical decompression of the Calcineurin-induced tremor is bilateral and may affect the abdominal compartment. hands and feet. Tacrolimus tremor is activated by action, but CT urography (Option B) is the diagnostic test of choice in about 50% of cases the tremor can be classified as both for patients with unexplained hematuria and allows char- an action and resting tremor. The tremor is associated with acterization of kidney tumors and cysts. MRI with contrast elevated drug levels and may be most pronounced when drug is an alternative for evaluation of kidney masses and cysts levels peak following a dose. This patient’s tacrolimus trough when CT cannot be performed. These imaging tests would measurement should be checked, as treatment interventions not be useful in this patient with acute kidney injury. > include dose reduction if permissible, conversion to long- Indications for kidney biopsy (Option C) include glo- = 7) acting formulations, addition of a §-blocker, or conversion merular hematuria, severely increased albuminuria, acute = to an alternate agent if the tremor is debilitating and unre- or chronic kidney disease of unclear cause (in the absence oO = 7.) sponsive to other interventions. These adjustments should of atrophic kidneys), and kidney transplant dysfunction or oy be made in conjunction with the patient’s nephrologist or monitoring. Bladder pressure measurement is indicated as = Qo. transplant program. Other side effects of calcineurin inhib- the next test because it is the most likely to provide a diag- (2) = itors include new-onset type 2 diabetes mellitus, decreased nosis, obviating the need for additional testing. re glomerular filtration rate, hypertension, dyslipidemia, and Kidney ultrasonography (Option D) is helpful to s) = gingival hyperplasia. exclude obstruction, but new bilateral ureteral obstruction @ wn Metoprolol (Option A) is not causing, and may be useful is not strongly suspected in this patient and the placement in treating, this patient’s tacrolimus-related tremor. of a bladder catheter rules out acute urethral obstruction. Side effects of mycophenolate mofetil (Option B) include nausea, vomiting, diarrhea, leukopenia, and ane- mia, but not tremor. e Abdominal compartment syndrome is defined as a Although glucocorticoids such as prednisone (Option sustained intra-abdominal pressure >20 mm Hg that C) cause a myriad of effects that may include psychological is associated with at least one organ dysfunction. distress and jumpiness, they do not cause tremor. Other side e The diagnosis of abdominal compartment syndrome effects associated with glucocorticoids include hyperten- can be confirmed through measurement of bladder sion, edema, new-onset type 2 diabetes, osteoporosis, and pressure via a bladder catheter as a surrogate for intra- osteonecrosis. abdominal pressure measurement.

Although glucocorticoids such as prednisone (Option sustained intra-abdominal pressure >20 mm Hg that C) cause a myriad of effects that may include psychological is associated with at least one organ dysfunction. distress and jumpiness, they do not cause tremor. Other side e The diagnosis of abdominal compartment syndrome effects associated with glucocorticoids include hyperten- can be confirmed through measurement of bladder sion, edema, new-onset type 2 diabetes, osteoporosis, and pressure via a bladder catheter as a surrogate for intra- osteonecrosis. abdominal pressure measurement. Bibliography ¢ Calcineurin inhibitor side effects include tremor, Patel DM, Connor MJ Jr. Intra-abdominal hypertension and abdominal new-onset type 2 diabetes mellitus, decreased glo- compartment syndrome: an underappreciated cause of acute kidney merular filtration rate, hypertension, dyslipidemia, injury. Adv Chronic Kidney Dis. 2016:23:160-166. [PMID: 27113692] doi:10.1053/j.ackd.2016.03.002 and gingival hyperplasia.

Bibliography ¢ Calcineurin inhibitor side effects include tremor, Patel DM, Connor MJ Jr. Intra-abdominal hypertension and abdominal new-onset type 2 diabetes mellitus, decreased glo- compartment syndrome: an underappreciated cause of acute kidney merular filtration rate, hypertension, dyslipidemia, injury. Adv Chronic Kidney Dis. 2016:23:160-166. [PMID: 27113692] doi:10.1053/j.ackd.2016.03.002 and gingival hyperplasia. Bibliography Item 60 Answer: D Erro R, Bacchin R, Magrinelli F, et al. Tremor induced by calcineurin inhibitor immunosuppression: a single-centre observational study in Educational Objective: Treat isovolemic hypernatremia. kidney transplanted patients. J Neurol. 2018;265:1676-1683. [PMID: 29777361] doi:10.1007/s00415-018-8904-x The most appropriate treatment for this patient’s hypernatre- mia is administration of water via nasogastric tube (Option D). Hyperglycemic hyperosmolar syndrome (HHS), an acute complication of type 2 diabetes mellitus, manifests as extreme Item 59 Answer: A hyperglycemia and must be treated early and aggressively Educational Objective: Diagnose abdominal to avoid life-threatening consequences from dehydration compartment syndrome. and electrolyte abnormalities. Extreme glucosuria causes an The most appropriate diagnostic test to perform next is blad- osmotic diuresis and severe volume depletion, which may der pressure measurement (Option A). This patient may have be exacerbated by gastrointestinal losses of volume and abdominal compartment syndrome (ACS), which is defined electrolytes. The condition may progress to lethargy, obtun- as a sustained intra-abdominal pressure >20 mm Hg that is dation, and death. Treatment includes vigorous hydration associated with at least one organ dysfunction. The diagno and insulin. This patient became hypernatremic because of sis of ACS should be considered in the setting of abdominal water loss during glucose-induced osmotic diuresis, Treat- surgery, trauma, intra-abdominal bleeding, ascites, bowel ment of his hyperglycemia with insulin caused a decrease in obstruction, ileus, or pancreatitis. It can also be caused by extracellular osmolality, causing water to move into cells. For

Bibliography Item 60 Answer: D Erro R, Bacchin R, Magrinelli F, et al. Tremor induced by calcineurin inhibitor immunosuppression: a single-centre observational study in Educational Objective: Treat isovolemic hypernatremia. kidney transplanted patients. J Neurol. 2018;265:1676-1683. [PMID: 29777361] doi:10.1007/s00415-018-8904-x The most appropriate treatment for this patient’s hypernatre- mia is administration of water via nasogastric tube (Option D). Hyperglycemic hyperosmolar syndrome (HHS), an acute complication of type 2 diabetes mellitus, manifests as extreme Item 59 Answer: A hyperglycemia and must be treated early and aggressively Educational Objective: Diagnose abdominal to avoid life-threatening consequences from dehydration compartment syndrome. and electrolyte abnormalities. Extreme glucosuria causes an The most appropriate diagnostic test to perform next is blad- osmotic diuresis and severe volume depletion, which may der pressure measurement (Option A). This patient may have be exacerbated by gastrointestinal losses of volume and abdominal compartment syndrome (ACS), which is defined electrolytes. The condition may progress to lethargy, obtun- as a sustained intra-abdominal pressure >20 mm Hg that is dation, and death. Treatment includes vigorous hydration associated with at least one organ dysfunction. The diagno and insulin. This patient became hypernatremic because of sis of ACS should be considered in the setting of abdominal water loss during glucose-induced osmotic diuresis, Treat- surgery, trauma, intra-abdominal bleeding, ascites, bowel ment of his hyperglycemia with insulin caused a decrease in obstruction, ileus, or pancreatitis. It can also be caused by extracellular osmolality, causing water to move into cells. For 150

Answers and Critiques C) every 100-mg/dL (5.6-mmol/L) decrease in serum glucose, lower extremity edema. A thiazide diuretic will unlikely be serum sodium will increase by approximately 2.0 mEq/L effective, as her estimated glomerular filtration rate is <30 mL/ CONT. * (2.0 mmol/L). This patient's water deficit is approximately min/1.73 m2. Therefore, a loop diuretic, such as furosemide, 4500 mL, making administration of water the most appropri- two or three times daily, is indicated for management of this ate treatment. Because this patient is confused, administra patient’s hypertension. Suboptimal blood pressure control in tion of water through nasogastric tube is the best approach; patients with sodium-retentive, edematous conditions, such otherwise, the patient could receive water orally. Although as advanced CKD, heart failure, and cirrhosis, is frequently the decreases of serum sodium up to 1.0 mEq/L (1.0 mmol/L) result of not including a diuretic, which ensures that extracel- per hour do not appear to have adverse effects, most author lular volume expansion is prevented or treated. ities recommend decreasing serum sodium by no more than Without a compelling indication such as heart failure 10 mEq/L (10 mmol/L) daily. Because of ongoing water losses, or recent myocardial infarction, the addition of a B-blocker the calculated rate of correction will be somewhat lower than such as carvedilol (Option A) to this patient’s treatment reg- the actual rate. imen is not appropriate. Additionally, a B-blocker will not 4] ” Administration of 5% dextrose (Option A) is as effec reduce this patient’s expanded extracellular volume, thus 3 > tive as water in treating hypernatremia. However, this limiting its ability to reduce the blood pressure. =] patient has hyperglycemia, and administration of a glucose- Similarly, hydralazine (Option C) is not indicated at = Oo containing solution may worsen it as well as increase free this time because it will likely increase the patient’s already =| iS water losses by inducing an osmotic diuresis. expanded extracellular volume, resulting in inadequate co

C) every 100-mg/dL (5.6-mmol/L) decrease in serum glucose, lower extremity edema. A thiazide diuretic will unlikely be serum sodium will increase by approximately 2.0 mEq/L effective, as her estimated glomerular filtration rate is <30 mL/ CONT. * (2.0 mmol/L). This patient's water deficit is approximately min/1.73 m2. Therefore, a loop diuretic, such as furosemide, 4500 mL, making administration of water the most appropri- two or three times daily, is indicated for management of this ate treatment. Because this patient is confused, administra patient’s hypertension. Suboptimal blood pressure control in tion of water through nasogastric tube is the best approach; patients with sodium-retentive, edematous conditions, such otherwise, the patient could receive water orally. Although as advanced CKD, heart failure, and cirrhosis, is frequently the decreases of serum sodium up to 1.0 mEq/L (1.0 mmol/L) result of not including a diuretic, which ensures that extracel- per hour do not appear to have adverse effects, most author lular volume expansion is prevented or treated. ities recommend decreasing serum sodium by no more than Without a compelling indication such as heart failure 10 mEq/L (10 mmol/L) daily. Because of ongoing water losses, or recent myocardial infarction, the addition of a B-blocker the calculated rate of correction will be somewhat lower than such as carvedilol (Option A) to this patient’s treatment reg- the actual rate. imen is not appropriate. Additionally, a B-blocker will not 4] ” Administration of 5% dextrose (Option A) is as effec reduce this patient’s expanded extracellular volume, thus 3 > tive as water in treating hypernatremia. However, this limiting its ability to reduce the blood pressure. =] patient has hyperglycemia, and administration of a glucose- Similarly, hydralazine (Option C) is not indicated at = Oo containing solution may worsen it as well as increase free this time because it will likely increase the patient’s already =| iS water losses by inducing an osmotic diuresis. expanded extracellular volume, resulting in inadequate co Although 0.45% normal saline (Option B) is hypotonic blood pressure control. wn oe ® and will correct this patient’s elevated serum sodium, a Although the patient has CKD and albuminuria, adding = minimum of 9 liters is necessary to decrease serum sodium lisinopril (Option D), an ACE inhibitor, to the patient’s anti- ~ = into the normal range. hypertensive medication regimen, which already includes =f

Although 0.45% normal saline (Option B) is hypotonic blood pressure control. wn oe ® and will correct this patient’s elevated serum sodium, a Although the patient has CKD and albuminuria, adding = minimum of 9 liters is necessary to decrease serum sodium lisinopril (Option D), an ACE inhibitor, to the patient’s anti- ~ = into the normal range. hypertensive medication regimen, which already includes =f The use of 0.9% saline (sodium concentration = 154 losartan, an ARB, is not the appropriate treatment. Combi- mEq/L [154 mmol/L]) (Option C) will not improve this nation therapy with an ACE inhibitor and ARB may result in patient’s hypernatremia. Furthermore, it will worsen his adverse events, such as acute kidney injury and hyperkale- already elevated blood pressure and further exacerbate mia, and does not improve cardiovascular outcomes com- his hyperchloremic metabolic acidosis. pared with treatment with an ACE inhibitor or ARB alone. e The treatment of isovolemic hypernatremia is water, e A loop diuretic such as furosemide is indicated for preferably orally or by nasogastric tube if the patient treating hypertension in patients with advanced is incapable of drinking. chronic kidney disease.

e The treatment of isovolemic hypernatremia is water, e A loop diuretic such as furosemide is indicated for preferably orally or by nasogastric tube if the patient treating hypertension in patients with advanced is incapable of drinking. chronic kidney disease. e The rate of correction of serum sodium for hyperna- tremia should be <l0 mEq/L (10 mmol/L) daily. Bibliography Kalaitzidis RG, Elisaf MS. Treatment of hypertension in chronic kidney disease. Curr Hypertens Rep. 2018;20:64. [PMID: 29892833] doi:10.1007/ Bibliography s11906-018-0864-0

e The rate of correction of serum sodium for hyperna- tremia should be <l0 mEq/L (10 mmol/L) daily. Bibliography Kalaitzidis RG, Elisaf MS. Treatment of hypertension in chronic kidney disease. Curr Hypertens Rep. 2018;20:64. [PMID: 29892833] doi:10.1007/ Bibliography s11906-018-0864-0 Overgaard-Steensen C, Ring T. Clinical review: practical approach to hyponatraemia and hypernatraemia in critically ill patients. Crit Care. 2013;17:206. [PMID: 23672688] doi:10.1186/cc11805 Item 62 Answer: A Educational Objective: Manage venous access for a Item 61 Answer: B patient with chronic kidney disease. Educational Objective: Treat hypertension with a loop Internal jugular vein insertion of a central venous catheter is diuretic in advanced chronic kidney disease. the most appropriate method of venous access for this patient The most appropriate additional treatment for this (Option A). Patients with advanced chronic kidney disease patient’s antihypertensive medication regimen is furosemide (CKD) may ultimately require renal replacement therapy. (Option B). ACE inhibitors or angiotensin receptor blockers Arteriovenous fistula (AVF) placement is the safest and most (ARBs) are first-line medications for patients with advanced enduring option for vascular access. AVFs have superior clini- chronic kidney disease (CKD) or proteinuric CKD. Calcium cal outcomes compared with arteriovenous grafts. Protecting channel blockers reduce albuminuria and slow the decline the veins of the nondominant arm is of paramount impor- in kidney function but should be combined with an ACE tance for the future success ofa functioning AVF and involves inhibitor or ARB. Diuretics are the backbone of hyperten- limiting phlebotomy and intravenous catheters in that arm. sion management in patients with CKD because of increased Peripherally inserted central catheters (PICCs) (Options extracellular volume. This patient has an elevated blood pres- B, C) are long catheters that are inserted peripherally and sure not controlled to a target goal of <130/80 mm Hg in the terminate in the central veins. PICCs are popular because of setting of stage G4 CKD and evidence of a sodium-retentive their ease of insertion and use. PICC lines can lead to signif state based on the presence of jugular venous distention and icant trauma and venous stenosis in the veins that may be

Overgaard-Steensen C, Ring T. Clinical review: practical approach to hyponatraemia and hypernatraemia in critically ill patients. Crit Care. 2013;17:206. [PMID: 23672688] doi:10.1186/cc11805 Item 62 Answer: A Educational Objective: Manage venous access for a Item 61 Answer: B patient with chronic kidney disease. Educational Objective: Treat hypertension with a loop Internal jugular vein insertion of a central venous catheter is diuretic in advanced chronic kidney disease. the most appropriate method of venous access for this patient The most appropriate additional treatment for this (Option A). Patients with advanced chronic kidney disease patient’s antihypertensive medication regimen is furosemide (CKD) may ultimately require renal replacement therapy. (Option B). ACE inhibitors or angiotensin receptor blockers Arteriovenous fistula (AVF) placement is the safest and most (ARBs) are first-line medications for patients with advanced enduring option for vascular access. AVFs have superior clini- chronic kidney disease (CKD) or proteinuric CKD. Calcium cal outcomes compared with arteriovenous grafts. Protecting channel blockers reduce albuminuria and slow the decline the veins of the nondominant arm is of paramount impor- in kidney function but should be combined with an ACE tance for the future success ofa functioning AVF and involves inhibitor or ARB. Diuretics are the backbone of hyperten- limiting phlebotomy and intravenous catheters in that arm. sion management in patients with CKD because of increased Peripherally inserted central catheters (PICCs) (Options extracellular volume. This patient has an elevated blood pres- B, C) are long catheters that are inserted peripherally and sure not controlled to a target goal of <130/80 mm Hg in the terminate in the central veins. PICCs are popular because of setting of stage G4 CKD and evidence of a sodium-retentive their ease of insertion and use. PICC lines can lead to signif state based on the presence of jugular venous distention and icant trauma and venous stenosis in the veins that may be 151

Ansand werCritrque s s used for AVF creation. This could impair blood flow through in three patients with anti-GBM antibody disease will have the fistula, impair maturation, and even lead to primary positive ANCA serologies, usually antimyeloperoxidase (MPO) CONT. nonfunctioning of the hemodialysis access. Data demon- antibodies, which can affect prognosis. Combined seropositiv- strate that PICC lines in either arm, placed before or after ini- ity is most commonly seen in patients with anti-GBM antibody tiation of hemodialysis, are independently associated with disease who are older women. Therefore, it is appropriate a 15% to 20% lower likelihood of transition to any working to test for p-ANCA/anti-MPO and c-ANCA/antiproteinase 3 fistula or graft. The long-term use of PICC lines is also associ- antibodies. Successful treatment, which typically includes ated with an increased risk for death. The American Society glucocorticoids, plasmapheresis, and cyclophosphamide, will of Nephrology recommends that PICC line catheters should eradicate the patient’s serum anti-GBM antibody titer. be avoided in patients with an estimated glomerular filtra- Testing for anti-double-stranded DNA antibodies tion rate <60 mL/min/1.73 m2. (Option A) is not required in this patient, as his antinuclear Avoidance of subclavian venous catheters (Option D) antibody test is negative and his kidney biopsy shows no > helps limit subclavian stenosis, which can impair the proper granular staining suggestive of lupus nephritis. = wv functioning of an arteriovenous access used for dialysis. Anti-phospholipase A2 receptor antibodies (Option C) = Although central lines inserted through the internal jugular @ can be checked in patients suspected of having primary og

used for AVF creation. This could impair blood flow through in three patients with anti-GBM antibody disease will have the fistula, impair maturation, and even lead to primary positive ANCA serologies, usually antimyeloperoxidase (MPO) CONT. nonfunctioning of the hemodialysis access. Data demon- antibodies, which can affect prognosis. Combined seropositiv- strate that PICC lines in either arm, placed before or after ini- ity is most commonly seen in patients with anti-GBM antibody tiation of hemodialysis, are independently associated with disease who are older women. Therefore, it is appropriate a 15% to 20% lower likelihood of transition to any working to test for p-ANCA/anti-MPO and c-ANCA/antiproteinase 3 fistula or graft. The long-term use of PICC lines is also associ- antibodies. Successful treatment, which typically includes ated with an increased risk for death. The American Society glucocorticoids, plasmapheresis, and cyclophosphamide, will of Nephrology recommends that PICC line catheters should eradicate the patient’s serum anti-GBM antibody titer. be avoided in patients with an estimated glomerular filtra- Testing for anti-double-stranded DNA antibodies tion rate <60 mL/min/1.73 m2. (Option A) is not required in this patient, as his antinuclear Avoidance of subclavian venous catheters (Option D) antibody test is negative and his kidney biopsy shows no > helps limit subclavian stenosis, which can impair the proper granular staining suggestive of lupus nephritis. = wv functioning of an arteriovenous access used for dialysis. Anti-phospholipase A2 receptor antibodies (Option C) = Although central lines inserted through the internal jugular @ can be checked in patients suspected of having primary og w vein are associated with central venous stenosis, a central membranous nephropathy, which typically presents with oY) = line is a better alternative than a PICC or subclavian insertion the nephrotic syndrome and preserved kidney function. The Qa of a central venous catheter; central lines are not inserted findings of erythrocytes and erythrocyte casts also argue iz) =. into a peripheral vein, which would be used for the creation against primary membranous nephropathy. =. of a hemodialysis site, and utilize a vessel not as prone to 2 IgA nephropathy (IgAN) can present with any of i= stenosis as the subclavian vein. @ the manifestations of the nephritic syndrome. Diagnosis wn can only be made when kidney biopsy shows dominant mesangial immune deposits of IgA with C3, and occasionally ¢ The American Society of Nephrology recommends IgG or IgM. Circulating IgA levels (Option D) are not diag- that peripherally inserted central catheter line cathe- nostically useful, nor can they be reliably correlated with ters should be avoided in patients with an estimated disease activity and should not be obtained. This patient’s glomerular filtration rate <60 mL/min/1.73 m2. kidney biopsy shows linear staining, which is not consistent with IgAN. Bibliography McGill RL, Ruthazer R, Meyer KB, et al. Peripherally inserted central cathe- ters and hemodialysis outcomes. Clin J Am Soc Nephrol. 2016;11:1434- e Anti-glomerular basement membrane antibody dis- 1440. [PMID: 27340280] doi:10.2215/CJN.01980216 ease is characterized by necrotizing and crescentic glomerulonephritis with linear staining for IgG on

w vein are associated with central venous stenosis, a central membranous nephropathy, which typically presents with oY) = line is a better alternative than a PICC or subclavian insertion the nephrotic syndrome and preserved kidney function. The Qa of a central venous catheter; central lines are not inserted findings of erythrocytes and erythrocyte casts also argue iz) =. into a peripheral vein, which would be used for the creation against primary membranous nephropathy. =. of a hemodialysis site, and utilize a vessel not as prone to 2 IgA nephropathy (IgAN) can present with any of i= stenosis as the subclavian vein. @ the manifestations of the nephritic syndrome. Diagnosis wn can only be made when kidney biopsy shows dominant mesangial immune deposits of IgA with C3, and occasionally ¢ The American Society of Nephrology recommends IgG or IgM. Circulating IgA levels (Option D) are not diag- that peripherally inserted central catheter line cathe- nostically useful, nor can they be reliably correlated with ters should be avoided in patients with an estimated disease activity and should not be obtained. This patient’s glomerular filtration rate <60 mL/min/1.73 m2. kidney biopsy shows linear staining, which is not consistent with IgAN. Bibliography McGill RL, Ruthazer R, Meyer KB, et al. Peripherally inserted central cathe- ters and hemodialysis outcomes. Clin J Am Soc Nephrol. 2016;11:1434- e Anti-glomerular basement membrane antibody dis- 1440. [PMID: 27340280] doi:10.2215/CJN.01980216 ease is characterized by necrotizing and crescentic glomerulonephritis with linear staining for IgG on Item 63 immunofluorescence. Answer: B Educational Objective: Diagnose anti-glomerular base- ¢ Measurement of anti-glomerular basement mem-

w vein are associated with central venous stenosis, a central membranous nephropathy, which typically presents with oY) = line is a better alternative than a PICC or subclavian insertion the nephrotic syndrome and preserved kidney function. The Qa of a central venous catheter; central lines are not inserted findings of erythrocytes and erythrocyte casts also argue iz) =. into a peripheral vein, which would be used for the creation against primary membranous nephropathy. =. of a hemodialysis site, and utilize a vessel not as prone to 2 IgA nephropathy (IgAN) can present with any of i= stenosis as the subclavian vein. @ the manifestations of the nephritic syndrome. Diagnosis wn can only be made when kidney biopsy shows dominant mesangial immune deposits of IgA with C3, and occasionally ¢ The American Society of Nephrology recommends IgG or IgM. Circulating IgA levels (Option D) are not diag- that peripherally inserted central catheter line cathe- nostically useful, nor can they be reliably correlated with ters should be avoided in patients with an estimated disease activity and should not be obtained. This patient’s glomerular filtration rate <60 mL/min/1.73 m2. kidney biopsy shows linear staining, which is not consistent with IgAN. Bibliography McGill RL, Ruthazer R, Meyer KB, et al. Peripherally inserted central cathe- ters and hemodialysis outcomes. Clin J Am Soc Nephrol. 2016;11:1434- e Anti-glomerular basement membrane antibody dis- 1440. [PMID: 27340280] doi:10.2215/CJN.01980216 ease is characterized by necrotizing and crescentic glomerulonephritis with linear staining for IgG on Item 63 immunofluorescence. Answer: B Educational Objective: Diagnose anti-glomerular base- ¢ Measurement of anti-glomerular basement mem- ment membrane antibody disease. brane (anti-GBM) antibodies confirm the diagnosis of anti-GBM antibody disease and are used to monitor The most appropriate serologic test to perform next is mea- response to treatment. surement of anti-glomerular basement membrane (anti- GBM) antibodies (Option B). This patient has rapidly pro- Bibliography gressive glomerulonephritis (RPGN), defined as an acute Gulati K, McAdoo SP. Anti-glomerular basement membrane disease. Rheum and steep rise in serum creatinine accompanied by hema- Dis Clin North Am. 2018;44:651-673. [PMID: 30274629] doi:10.1016/j. turia and proteinuria. The differential diagnosis for RPGN is rdc.2018.06.011

ment membrane antibody disease. brane (anti-GBM) antibodies confirm the diagnosis of anti-GBM antibody disease and are used to monitor The most appropriate serologic test to perform next is mea- response to treatment. surement of anti-glomerular basement membrane (anti- GBM) antibodies (Option B). This patient has rapidly pro- Bibliography gressive glomerulonephritis (RPGN), defined as an acute Gulati K, McAdoo SP. Anti-glomerular basement membrane disease. Rheum and steep rise in serum creatinine accompanied by hema- Dis Clin North Am. 2018;44:651-673. [PMID: 30274629] doi:10.1016/j. turia and proteinuria. The differential diagnosis for RPGN is rdc.2018.06.011 divided histologically into three patterns on immunofluo- rescence microscopy of the kidney biopsy: pauci-immune Item 64 Answer: A staining (ANCA-mediated glomerulonephritis), linear stain- ing (anti-GBM glomerulonephritis), and granular staining Educational Objective: Diagnose IgG4-related disease.

divided histologically into three patterns on immunofluo- rescence microscopy of the kidney biopsy: pauci-immune Item 64 Answer: A staining (ANCA-mediated glomerulonephritis), linear stain- ing (anti-GBM glomerulonephritis), and granular staining Educational Objective: Diagnose IgG4-related disease. (lupus nephritis). This patient has RPGN and a kidney biopsy The most likely diagnosis is IgG4-related disease (IgG4-RD) showing linear staining, which is seen in anti-GBM antibody (Option A), which is typically characterized by infiltration disease. Lung involvement (Goodpasture syndrome) occurs in and tumefaction of the affected tissue with resultant organ >50% of patients with anti-GBM antibody disease; hemoptysis enlargement, fibrosis, and dysfunction. Patients commonly can be a presenting symptom, although shortness of breath present with a sentinel organ enlargement, but careful eval- or cough should also raise suspicion for a pulmonary-renal uation often reveals more extensive disease. Some common syndrome even in the absence of hemoptysis. Testing for anti- presentations of IgG4-RD include idiopathic pancreatitis, GBM antibodies is required as the next step in management to sclerosing cholangitis, bilateral salivary and/or lacrimal gland confirm diagnosis. For this patient, anti-GBM antibody titers enlargement, retroperitoneal fibrosis, orbital pseudotumor, would also be used to monitor treatment response. Up to one or proptosis. Diagnosis is made by tissue biopsy, which

(lupus nephritis). This patient has RPGN and a kidney biopsy The most likely diagnosis is IgG4-related disease (IgG4-RD) showing linear staining, which is seen in anti-GBM antibody (Option A), which is typically characterized by infiltration disease. Lung involvement (Goodpasture syndrome) occurs in and tumefaction of the affected tissue with resultant organ >50% of patients with anti-GBM antibody disease; hemoptysis enlargement, fibrosis, and dysfunction. Patients commonly can be a presenting symptom, although shortness of breath present with a sentinel organ enlargement, but careful eval- or cough should also raise suspicion for a pulmonary-renal uation often reveals more extensive disease. Some common syndrome even in the absence of hemoptysis. Testing for anti- presentations of IgG4-RD include idiopathic pancreatitis, GBM antibodies is required as the next step in management to sclerosing cholangitis, bilateral salivary and/or lacrimal gland confirm diagnosis. For this patient, anti-GBM antibody titers enlargement, retroperitoneal fibrosis, orbital pseudotumor, would also be used to monitor treatment response. Up to one or proptosis. Diagnosis is made by tissue biopsy, which 152

_ NEES ME Ghbgues demonstrates a dense lymphoplasmacytic infiltrate, CD4- hyponatremia (serum osmolality, 275-295 mOsm/kg H,O) is positive T cells and plasma cells in germinal centers, a laboratory artifact caused by the method by which serum IgG4-staining plasma cells, storiform fibrosis, obliterative sodium is measured. Plasma is divided into a water phase phlebitis or arteritis, and tissue eosinophilia. IgG4 levels are (93%), in which the sodium is dissolved, and a solid phase elevated in the serum in 70% to 80% of patients; therefore, a (7%), which consists of lipids and proteins. If the solid phase normal serum IgG4 level does not rule out the disease. Initial is increased by an increase in proteins, such as those found in treatment is prednisone. In this patient, clues to the underly- multiple myeloma or severe elevations in serum triglycerides, ing diagnosis are the presence of idiopathic pancreatitis and there is a decrease in the water phase (i.e., from 93% to 80%). large kidney size for a patient with chronic kidney disease. Most laboratories use a diluting electrode in which there is a Kidney involvement of IgG4-RD typically manifests as chronic tenfold dilution of the specimen when measuring electrolytes. interstitial nephritis (CIN) with fibrosis; plasma cells typically With a decrease in the aqueous phase, the dilution is no longer stain positive for IgG4. 1:10, but even greater, resulting in a spurious value for sodium. Sarcoidosis (Option B) is most commonly characterized Hypercalcemia (Option A) can cause polyuria sec- wn rt by noncaseating granulomas and CIN changes on biopsy. ondary to nephrogenic diabetes insipidus, which would s

demonstrates a dense lymphoplasmacytic infiltrate, CD4- hyponatremia (serum osmolality, 275-295 mOsm/kg H,O) is positive T cells and plasma cells in germinal centers, a laboratory artifact caused by the method by which serum IgG4-staining plasma cells, storiform fibrosis, obliterative sodium is measured. Plasma is divided into a water phase phlebitis or arteritis, and tissue eosinophilia. IgG4 levels are (93%), in which the sodium is dissolved, and a solid phase elevated in the serum in 70% to 80% of patients; therefore, a (7%), which consists of lipids and proteins. If the solid phase normal serum IgG4 level does not rule out the disease. Initial is increased by an increase in proteins, such as those found in treatment is prednisone. In this patient, clues to the underly- multiple myeloma or severe elevations in serum triglycerides, ing diagnosis are the presence of idiopathic pancreatitis and there is a decrease in the water phase (i.e., from 93% to 80%). large kidney size for a patient with chronic kidney disease. Most laboratories use a diluting electrode in which there is a Kidney involvement of IgG4-RD typically manifests as chronic tenfold dilution of the specimen when measuring electrolytes. interstitial nephritis (CIN) with fibrosis; plasma cells typically With a decrease in the aqueous phase, the dilution is no longer stain positive for IgG4. 1:10, but even greater, resulting in a spurious value for sodium. Sarcoidosis (Option B) is most commonly characterized Hypercalcemia (Option A) can cause polyuria sec- wn rt by noncaseating granulomas and CIN changes on biopsy. ondary to nephrogenic diabetes insipidus, which would s Sarcoidosis does not explain this patient’s episodes of idio- increase the sodium concentration, not lower it, as seen in — pathic pancreatitis or the lymphoplasmacytic cell infiltrate this patient. I a on kidney biopsy. Because the kidney requires solute to excrete water, a so = Systemic lupus erythematosus (SLE) (Option C) may decrease in solute intake (Option C), which occurs in poto- ©

Sarcoidosis does not explain this patient’s episodes of idio- increase the sodium concentration, not lower it, as seen in — pathic pancreatitis or the lymphoplasmacytic cell infiltrate this patient. I a on kidney biopsy. Because the kidney requires solute to excrete water, a so = Systemic lupus erythematosus (SLE) (Option C) may decrease in solute intake (Option C), which occurs in poto- © present with CIN. However, SLE more frequently manifests mania (excessive beer drinking) or in individuals with star- w a o in the kidney as acute glomerular disease and is not associ- vation, the kidney’s ability to excrete water is reduced and = ated with pancreatitis or lymphoplasmacytic cell infiltrate can result in hyponatremia without excessive water intake. wn = on kidney biopsy. In these cases, urine osmolality would be <100 mOsm/kg 4

present with CIN. However, SLE more frequently manifests mania (excessive beer drinking) or in individuals with star- w a o in the kidney as acute glomerular disease and is not associ- vation, the kidney’s ability to excrete water is reduced and = ated with pancreatitis or lymphoplasmacytic cell infiltrate can result in hyponatremia without excessive water intake. wn = on kidney biopsy. In these cases, urine osmolality would be <100 mOsm/kg 4 Tubulointerstitial nephritis with uveitis (TINU) (Option H,0. D) is a distinct syndrome of acute interstitial nephritis with In psychogenic polydipsia (Option D), excess water features of uveitis and may be accompanied by various auto- intake exceeds the kidney’s ability to excrete water through antibodies and hypocomplementemia. Most patients with the urine, and urine osmolality would likely be <100 mOsm/ TINU are adolescents and young women. This patient’s clin- kg H,O. ical syndrome is not consistent with TINU. In the syndrome of inappropriate antidiuretic hormone (SIADH) secretion (Option E), the measured serum osmo- lality is always low, unlike that seen in this patient. Further- e Patients with IgG4-related disease commonly present more, patients with SIADH have hypo-osmolar hyponatre- with a sentinel organ enlargement and dysfunction, mia.

Tubulointerstitial nephritis with uveitis (TINU) (Option H,0. D) is a distinct syndrome of acute interstitial nephritis with In psychogenic polydipsia (Option D), excess water features of uveitis and may be accompanied by various auto- intake exceeds the kidney’s ability to excrete water through antibodies and hypocomplementemia. Most patients with the urine, and urine osmolality would likely be <100 mOsm/ TINU are adolescents and young women. This patient’s clin- kg H,O. ical syndrome is not consistent with TINU. In the syndrome of inappropriate antidiuretic hormone (SIADH) secretion (Option E), the measured serum osmo- lality is always low, unlike that seen in this patient. Further- e Patients with IgG4-related disease commonly present more, patients with SIADH have hypo-osmolar hyponatre- with a sentinel organ enlargement and dysfunction, mia. but careful evaluation often reveals more extensive disease. ¢ The first step in evaluating a patient with hypona- e Kidney involvement of IgG4-related disease typically tremia is to measure serum osmolality. manifests as chronic interstitial nephritis with fibrosis and dense lymphoplasmacytic infiltrate. e Isotonic hyponatremia is a laboratory artifact caused by increased plasma concentrations of lipids or proteins.

but careful evaluation often reveals more extensive disease. ¢ The first step in evaluating a patient with hypona- e Kidney involvement of IgG4-related disease typically tremia is to measure serum osmolality. manifests as chronic interstitial nephritis with fibrosis and dense lymphoplasmacytic infiltrate. e Isotonic hyponatremia is a laboratory artifact caused by increased plasma concentrations of lipids or proteins. Bibliography Zhang P, Cornell LD. IgG4-related tubulointerstitial nephritis. Adv Chronic Bibliography Kidney Dis. 2017;24:94-100. [PMID: 28284385] doi:10.1053/j.ackd. Katrangi W, Baumann NA, Nett RC, et al. Prevalence of clinically significant 2016.12.001 differences in sodium measurements due to abnormal protein concen- trations using an indirect ion-selective electrode method. J Appl Lab Med. 2019;4:427-432. [PMID: 31659081] doi:10.1373/jalm.2018.028720 Item 65 Answer: B

Bibliography Zhang P, Cornell LD. IgG4-related tubulointerstitial nephritis. Adv Chronic Bibliography Kidney Dis. 2017;24:94-100. [PMID: 28284385] doi:10.1053/j.ackd. Katrangi W, Baumann NA, Nett RC, et al. Prevalence of clinically significant 2016.12.001 differences in sodium measurements due to abnormal protein concen- trations using an indirect ion-selective electrode method. J Appl Lab Med. 2019;4:427-432. [PMID: 31659081] doi:10.1373/jalm.2018.028720 Item 65 Answer: B Educational Objective: Identify multiple myeloma as a cause of isotonic hyponatremia. Item 66 Answer: D Educational Objective: Diagnose surreptitious vomiting The most likely cause of this patient’s hyponatremia is multiple as a cause of metabolic alkalosis. myeloma (Option B). Results of this patient’s laboratory stud- ies, including elevated serum calcium, anemia, and elevated The most likely cause of this patient’s metabolic alkalosis is total protein and low albumin suggesting an increased gamma surreptitious vomiting (Option D). Metabolic alkalosis is diag- globulin fraction, support the diagnosis of multiple myeloma. nosed by an elevation in serum bicarbonate concentration The key finding, however, is that the patient has a normal mea- and elevated serum pH. This disorder is caused by either a loss sured serum osmolality in the context of hyponatremia. When of acid or administration or retention of bicarbonate. Condi- evaluating a patient with hyponatremia, the first step is to tions that contribute to the maintenance of metabolic alkalosis measure serum osmolality. In this patient, the serum osmolal- include volume contraction, ineffective arterial blood volume, ity is normal, and thus he has isotonic hyponatremia. Isotonic hypokalemia, chloride depletion, and decreased glomerular

Educational Objective: Identify multiple myeloma as a cause of isotonic hyponatremia. Item 66 Answer: D Educational Objective: Diagnose surreptitious vomiting The most likely cause of this patient’s hyponatremia is multiple as a cause of metabolic alkalosis. myeloma (Option B). Results of this patient’s laboratory stud- ies, including elevated serum calcium, anemia, and elevated The most likely cause of this patient’s metabolic alkalosis is total protein and low albumin suggesting an increased gamma surreptitious vomiting (Option D). Metabolic alkalosis is diag- globulin fraction, support the diagnosis of multiple myeloma. nosed by an elevation in serum bicarbonate concentration The key finding, however, is that the patient has a normal mea- and elevated serum pH. This disorder is caused by either a loss sured serum osmolality in the context of hyponatremia. When of acid or administration or retention of bicarbonate. Condi- evaluating a patient with hyponatremia, the first step is to tions that contribute to the maintenance of metabolic alkalosis measure serum osmolality. In this patient, the serum osmolal- include volume contraction, ineffective arterial blood volume, ity is normal, and thus he has isotonic hyponatremia. Isotonic hypokalemia, chloride depletion, and decreased glomerular 153

Answers and Critiques filtration. Laboratory evaluation of metabolic alkalosis is based kidney ultrasound indicate that he has had advanced chronic on urine chloride concentration. Metabolic alkalosis is consid- kidney disease (CKD), likely for years. When patients present ered saline responsive when associated with true hypovolemia with “acute” kidney injury, a late presentation of end-stage and responds to correction of the volume deficit with isotonic kidney disease (ESKD) must be part of the differential diagno- saline. Saline-responsive metabolic alkalosis presents with a sis. History, physical examination, and laboratory indices may low urine chloride of <15 mEq/L (15 mmol/L); the most com- not be able to distinguish between acute and chronic disease. mon causes are vomiting, nasogastric suction, and diuretic However, the ultrasound finding of small echogenic kidneys use. Hypokalemia in these circumstances occur secondarily is very consistent with advanced CKD. Initiation of dialysis for due to aldosterone elevation and cation loss as the kidney symptoms of uremia and severe metabolic acidosis is the most attempts to lose bicarbonate. Although these patients are usu- appropriate next step for this patient, regardless of the cause ally hypovolemic or normovolemic (with normal or low blood or duration of his kidney disease. pressures), patients with preexisting chronic hypertension A rapid volume challenge through intravenous 0.9% Pa may present with high to normal blood pressures. saline (Option B) is most appropriate for patients with acute = wn Bartter syndrome (Option A) and Gitelman syndrome prerenal kidney injury, but it may provoke heart failure in = are autosomal recessive genetic disorders of renal sodium this patient with ESKD. o = nn and chloride transporters that clinically mimic loop diuretic Intravenous high-dose glucocorticoids such as methyl pe¥) s and thiazide diuretic use, respectively. Both syndromes prednisolone (Option C) are initiated for patients with acute 2. present with hypokalemic alkalosis with urine chloride glomerulonephritis with rapid decline in kidney function; (m) me (>15 mEq/L [15 mmol/L]); therefore, neither syndrome is the this therapy would not be efficacious in patients, such as this me diagnosis in this case. one, with advanced CKD. 2 }oo The presence of hypertension, metabolic alkalosis, A percutaneous kidney biopsy (Option D) is indicated Oo nn and hypokalemia suggests elevated aldosterone states such only if a reversible or treatable cause of kidney disease is as Cushing syndrome and primary hyperaldosteronism suspected, but it is not helpful or practical in patients with (Options B, C). However, the presence of a low urine chlo- small echogenic kidneys that indicate irreversible kidney ride (<15 mEq/L [15 mmol/L]) in this patient rules out these disease. Finally, percutaneous kidney biopsy is relatively diagnoses. Patients with high urine chloride (+15 mEq/L contraindicated in patients with small kidneys because of [15 mmol/L]), elevated blood pressure, and hypokale- increased risk for bleeding. mia who do not appear to be overtly volume overloaded should be evaluated for a mineralocorticoid excess disorder (saline-resistant metabolic alkalosis) such as Cushing syn- e When patients present with presumed acute kidney

filtration. Laboratory evaluation of metabolic alkalosis is based kidney ultrasound indicate that he has had advanced chronic on urine chloride concentration. Metabolic alkalosis is consid- kidney disease (CKD), likely for years. When patients present ered saline responsive when associated with true hypovolemia with “acute” kidney injury, a late presentation of end-stage and responds to correction of the volume deficit with isotonic kidney disease (ESKD) must be part of the differential diagno- saline. Saline-responsive metabolic alkalosis presents with a sis. History, physical examination, and laboratory indices may low urine chloride of <15 mEq/L (15 mmol/L); the most com- not be able to distinguish between acute and chronic disease. mon causes are vomiting, nasogastric suction, and diuretic However, the ultrasound finding of small echogenic kidneys use. Hypokalemia in these circumstances occur secondarily is very consistent with advanced CKD. Initiation of dialysis for due to aldosterone elevation and cation loss as the kidney symptoms of uremia and severe metabolic acidosis is the most attempts to lose bicarbonate. Although these patients are usu- appropriate next step for this patient, regardless of the cause ally hypovolemic or normovolemic (with normal or low blood or duration of his kidney disease. pressures), patients with preexisting chronic hypertension A rapid volume challenge through intravenous 0.9% Pa may present with high to normal blood pressures. saline (Option B) is most appropriate for patients with acute = wn Bartter syndrome (Option A) and Gitelman syndrome prerenal kidney injury, but it may provoke heart failure in = are autosomal recessive genetic disorders of renal sodium this patient with ESKD. o = nn and chloride transporters that clinically mimic loop diuretic Intravenous high-dose glucocorticoids such as methyl pe¥) s and thiazide diuretic use, respectively. Both syndromes prednisolone (Option C) are initiated for patients with acute 2. present with hypokalemic alkalosis with urine chloride glomerulonephritis with rapid decline in kidney function; (m) me (>15 mEq/L [15 mmol/L]); therefore, neither syndrome is the this therapy would not be efficacious in patients, such as this me diagnosis in this case. one, with advanced CKD. 2 }oo The presence of hypertension, metabolic alkalosis, A percutaneous kidney biopsy (Option D) is indicated Oo nn and hypokalemia suggests elevated aldosterone states such only if a reversible or treatable cause of kidney disease is as Cushing syndrome and primary hyperaldosteronism suspected, but it is not helpful or practical in patients with (Options B, C). However, the presence of a low urine chlo- small echogenic kidneys that indicate irreversible kidney ride (<15 mEq/L [15 mmol/L]) in this patient rules out these disease. Finally, percutaneous kidney biopsy is relatively diagnoses. Patients with high urine chloride (+15 mEq/L contraindicated in patients with small kidneys because of [15 mmol/L]), elevated blood pressure, and hypokale- increased risk for bleeding. mia who do not appear to be overtly volume overloaded should be evaluated for a mineralocorticoid excess disorder (saline-resistant metabolic alkalosis) such as Cushing syn- e When patients present with presumed acute kidney drome and primary hyperaldosteronism. injury, a late presentation of end-stage kidney disease must be part of the differential diagnosis.

filtration. Laboratory evaluation of metabolic alkalosis is based kidney ultrasound indicate that he has had advanced chronic on urine chloride concentration. Metabolic alkalosis is consid- kidney disease (CKD), likely for years. When patients present ered saline responsive when associated with true hypovolemia with “acute” kidney injury, a late presentation of end-stage and responds to correction of the volume deficit with isotonic kidney disease (ESKD) must be part of the differential diagno- saline. Saline-responsive metabolic alkalosis presents with a sis. History, physical examination, and laboratory indices may low urine chloride of <15 mEq/L (15 mmol/L); the most com- not be able to distinguish between acute and chronic disease. mon causes are vomiting, nasogastric suction, and diuretic However, the ultrasound finding of small echogenic kidneys use. Hypokalemia in these circumstances occur secondarily is very consistent with advanced CKD. Initiation of dialysis for due to aldosterone elevation and cation loss as the kidney symptoms of uremia and severe metabolic acidosis is the most attempts to lose bicarbonate. Although these patients are usu- appropriate next step for this patient, regardless of the cause ally hypovolemic or normovolemic (with normal or low blood or duration of his kidney disease. pressures), patients with preexisting chronic hypertension A rapid volume challenge through intravenous 0.9% Pa may present with high to normal blood pressures. saline (Option B) is most appropriate for patients with acute = wn Bartter syndrome (Option A) and Gitelman syndrome prerenal kidney injury, but it may provoke heart failure in = are autosomal recessive genetic disorders of renal sodium this patient with ESKD. o = nn and chloride transporters that clinically mimic loop diuretic Intravenous high-dose glucocorticoids such as methyl pe¥) s and thiazide diuretic use, respectively. Both syndromes prednisolone (Option C) are initiated for patients with acute 2. present with hypokalemic alkalosis with urine chloride glomerulonephritis with rapid decline in kidney function; (m) me (>15 mEq/L [15 mmol/L]); therefore, neither syndrome is the this therapy would not be efficacious in patients, such as this me diagnosis in this case. one, with advanced CKD. 2 }oo The presence of hypertension, metabolic alkalosis, A percutaneous kidney biopsy (Option D) is indicated Oo nn and hypokalemia suggests elevated aldosterone states such only if a reversible or treatable cause of kidney disease is as Cushing syndrome and primary hyperaldosteronism suspected, but it is not helpful or practical in patients with (Options B, C). However, the presence of a low urine chlo- small echogenic kidneys that indicate irreversible kidney ride (<15 mEq/L [15 mmol/L]) in this patient rules out these disease. Finally, percutaneous kidney biopsy is relatively diagnoses. Patients with high urine chloride (+15 mEq/L contraindicated in patients with small kidneys because of [15 mmol/L]), elevated blood pressure, and hypokale- increased risk for bleeding. mia who do not appear to be overtly volume overloaded should be evaluated for a mineralocorticoid excess disorder (saline-resistant metabolic alkalosis) such as Cushing syn- e When patients present with presumed acute kidney drome and primary hyperaldosteronism. injury, a late presentation of end-stage kidney disease must be part of the differential diagnosis. ¢ History, physical examination, and laboratory indices e Saline-responsive metabolic alkalosis presents with a often do not discriminate between acute and chronic low urine chloride of <15 mEq/L (15 mmol/L); the kidney disease (CKD); however, small (<10 cm) echo- most common causes are vomiting, nasogastric suc- genic kidneys on ultrasound is very consistent with tion, and diuretic use. advanced CKD. e Patients with high urine chloride (+15 mEq/L [15 mmol/L]), hypertension, and hypokalemia who do Bibliography not appear to be overtly volume overloaded should be Levey AS, James MT. Acute kidney injury. Ann Intern Med. 2017;167:ITC66- evaluated for a mineralocorticoid excess disorder ITC80. [PMID: 29114754] doi:10.7326/AITC201711070

¢ History, physical examination, and laboratory indices e Saline-responsive metabolic alkalosis presents with a often do not discriminate between acute and chronic low urine chloride of <15 mEq/L (15 mmol/L); the kidney disease (CKD); however, small (<10 cm) echo- most common causes are vomiting, nasogastric suc- genic kidneys on ultrasound is very consistent with tion, and diuretic use. advanced CKD. e Patients with high urine chloride (+15 mEq/L [15 mmol/L]), hypertension, and hypokalemia who do Bibliography not appear to be overtly volume overloaded should be Levey AS, James MT. Acute kidney injury. Ann Intern Med. 2017;167:ITC66- evaluated for a mineralocorticoid excess disorder ITC80. [PMID: 29114754] doi:10.7326/AITC201711070 (saline-resistant metabolic alkalosis) such as Cushing syndrome and primary hyperaldosteronism. Item 68 Answer: B Bibliography Educational Objective: Adjust an antihypertensive Soifer JT, Kim HT. Approach to metabolic alkalosis. Emerg Med Clin North medication regimen using combination drug therapy. Am. 2014;32:453-63. [PMID: 24766943] doi:10.1016/j.emc.2014.01.005

(saline-resistant metabolic alkalosis) such as Cushing syndrome and primary hyperaldosteronism. Item 68 Answer: B Bibliography Educational Objective: Adjust an antihypertensive Soifer JT, Kim HT. Approach to metabolic alkalosis. Emerg Med Clin North medication regimen using combination drug therapy. Am. 2014;32:453-63. [PMID: 24766943] doi:10.1016/j.emc.2014.01.005 The most appropriate additional treatment is amlodipine, a calcium channel blocker (CCB) (Option B). This patient Item 67 Answer: A with hypertension requires escalation of her antihypertensive medication regimen because her blood pressure (BP) is not Educational Objective: Manage end-stage kidney disease at target. The 2017 American College of Cardiology/Ameri- with dialysis. can Heart Association BP guideline recommends a BP target The most appropriate management is to initiate dialysis of <130/80 mm Hg. Two strategies can be used: maximize (Option A). The history and physical examination findings medication dose before adding another agent or add another suggest that this patient has had long-standing uncontrolled agent from a different class of medication before maximizing hypertension. The small (<9 cm) echogenic kidneys seen on the dose of the prior agents. There are no randomized trials 154

_ Answers and Critiques comparing these strategies. Generally, there is diminishing ultrasonography does not expose patients to radiation and is return in BP lowering if dose is titrated up from 50% to 100% typically more readily available and has a lower cost compared of maximum. Also, it is unlikely that increasing the dose of a with CT; it is also the preferred modality during pregnancy. drug from 50% to 100% of maximum will result in a signifi- A positive ultrasound may therefore be adequate for initial cant BP reduction. Finally, titration to maximum doses more diagnosis in patients with a typical presentation for kidney commonly results in side effects and may reduce medication stones; more complex testing is indicated for those with a adherence. Therefore, adding a third drug to a two-drug regi- high clinical suspicion but a nondiagnostic ultrasound or a men is a strategy recommended by many experts. more complicated clinical presentation. Two drugs from classes that target the same BP con- Abdominal MRI (Option A) can be used during preg- trol system are less effective and potentially harmful when nancy, but it is not optimal for imaging kidney stones. Ultra- used together. For example, administration of combination sonography is preferred, although MRI may be a diagnostic therapy with renin-angiotensin system blockers, such as an option if additional imaging is required for diagnosis. ACE inhibitor with an angiotensin receptor blocker (ARB) Plain abdominal radiography (Option C) has limited util- wn @ or an ACE inhibitor or ARB with the direct renin inhibitor ity due to its inability to detect radiolucent uric acid stones, a

comparing these strategies. Generally, there is diminishing ultrasonography does not expose patients to radiation and is return in BP lowering if dose is titrated up from 50% to 100% typically more readily available and has a lower cost compared of maximum. Also, it is unlikely that increasing the dose of a with CT; it is also the preferred modality during pregnancy. drug from 50% to 100% of maximum will result in a signifi- A positive ultrasound may therefore be adequate for initial cant BP reduction. Finally, titration to maximum doses more diagnosis in patients with a typical presentation for kidney commonly results in side effects and may reduce medication stones; more complex testing is indicated for those with a adherence. Therefore, adding a third drug to a two-drug regi- high clinical suspicion but a nondiagnostic ultrasound or a men is a strategy recommended by many experts. more complicated clinical presentation. Two drugs from classes that target the same BP con- Abdominal MRI (Option A) can be used during preg- trol system are less effective and potentially harmful when nancy, but it is not optimal for imaging kidney stones. Ultra- used together. For example, administration of combination sonography is preferred, although MRI may be a diagnostic therapy with renin-angiotensin system blockers, such as an option if additional imaging is required for diagnosis. ACE inhibitor with an angiotensin receptor blocker (ARB) Plain abdominal radiography (Option C) has limited util- wn @ or an ACE inhibitor or ARB with the direct renin inhibitor ity due to its inability to detect radiolucent uric acid stones, a and it does not provide as much anatomic information as a aliskiren, increases cardiovascular and renal risk. Therefore, = aliskiren should not be added (Option A). other modalities; furthermore, it should be avoided during rs) Hydralazine (Option C) is not the best option, because pregnancy. However, it may be useful in assessing stone bur- sc = agents shown to reduce clinical events (such as thiazide den in nonpregnant patients with known radiopaque stones. cs

and it does not provide as much anatomic information as a aliskiren, increases cardiovascular and renal risk. Therefore, = aliskiren should not be added (Option A). other modalities; furthermore, it should be avoided during rs) Hydralazine (Option C) is not the best option, because pregnancy. However, it may be useful in assessing stone bur- sc = agents shown to reduce clinical events (such as thiazide den in nonpregnant patients with known radiopaque stones. cs diuretics, calcium channel blockers, ACE inhibitors, ARBs) Noncontrast helical abdominal CT (Option D) has tra- rn — o should be used preferentially. Additionally, it is a thrice-daily ditionally been the most commonly used imaging technique = nn medication. Use of longer-acting antihypertensive drugs because it detects most stones, provides anatomic infor- = mation, and visualizes the entire urinary tract; it may also <t that only require once-daily dosing and combination pills to reduce pill burden can increase adherence. suggest stone composition and potentially provide alterna- Adding hydrochlorothiazide (Option D) is not the best tive diagnoses if nephrolithiasis is not detected. Although option because two thiazide diuretics will not improve BP CT is more sensitive and specific than ultrasonography, a control in this patient and risks the development of hypokale- randomized controlled trial demonstrated equivalent diag- mia. However, concomitant use of diuretics that have different nostic accuracy within the emergency department. Finally, mechanisms of action, such as a combination of a thiazide CT is associated with significant radiation exposure and is diuretic, potassium-sparing diuretic, and/or a loop diuretic, contraindicated in pregnant women. can effectively control extracellular volume and hypertension. Ureteroscopy (Option E), in which an endoscopic device is introduced in a retrograde fashion into the ureter through the bladder, is most commonly used in the management of e Two strategies can be used for antihypertensive dose mid-ureteral and distal ureteral stones, using a combina- adjustment in the treatment of hypertension: maxi- tion of catheter-based stone disintegration methods (such mize medication dose before adding another agent or as laser lithotripsy), stone baskets, and ureteral stent place- add another agent before maximizing the dose of the ment. Although this procedure does not involve radiation, it prior agents. is not a diagnostic procedure indicated for suspected kidney stones because it is unnecessarily invasive. e Two drugs from classes that target the same blood pressure control system are less effective and poten- tially harmful when used together. e Ultrasonography is readily available, inexpensive, and very safe and is a useful first study in evaluating neph- Bibliography rolithiasis. Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. [PMID: 31060074] doi:10.7326/AITC201905070 e Kidney ultrasonography is the preferred diagnostic test for suspected nephrolithiasis in pregnant women.

diuretics, calcium channel blockers, ACE inhibitors, ARBs) Noncontrast helical abdominal CT (Option D) has tra- rn — o should be used preferentially. Additionally, it is a thrice-daily ditionally been the most commonly used imaging technique = nn medication. Use of longer-acting antihypertensive drugs because it detects most stones, provides anatomic infor- = mation, and visualizes the entire urinary tract; it may also <t that only require once-daily dosing and combination pills to reduce pill burden can increase adherence. suggest stone composition and potentially provide alterna- Adding hydrochlorothiazide (Option D) is not the best tive diagnoses if nephrolithiasis is not detected. Although option because two thiazide diuretics will not improve BP CT is more sensitive and specific than ultrasonography, a control in this patient and risks the development of hypokale- randomized controlled trial demonstrated equivalent diag- mia. However, concomitant use of diuretics that have different nostic accuracy within the emergency department. Finally, mechanisms of action, such as a combination of a thiazide CT is associated with significant radiation exposure and is diuretic, potassium-sparing diuretic, and/or a loop diuretic, contraindicated in pregnant women. can effectively control extracellular volume and hypertension. Ureteroscopy (Option E), in which an endoscopic device is introduced in a retrograde fashion into the ureter through the bladder, is most commonly used in the management of e Two strategies can be used for antihypertensive dose mid-ureteral and distal ureteral stones, using a combina- adjustment in the treatment of hypertension: maxi- tion of catheter-based stone disintegration methods (such mize medication dose before adding another agent or as laser lithotripsy), stone baskets, and ureteral stent place- add another agent before maximizing the dose of the ment. Although this procedure does not involve radiation, it prior agents. is not a diagnostic procedure indicated for suspected kidney stones because it is unnecessarily invasive. e Two drugs from classes that target the same blood pressure control system are less effective and poten- tially harmful when used together. e Ultrasonography is readily available, inexpensive, and very safe and is a useful first study in evaluating neph- Bibliography rolithiasis. Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. [PMID: 31060074] doi:10.7326/AITC201905070 e Kidney ultrasonography is the preferred diagnostic test for suspected nephrolithiasis in pregnant women. Item 69 Answer: B Bibliography Brisbane W, Bailey MR, Sorensen MD. An overview of kidney stone imaging Educational Objective: Diagnose nephrolithiasis during techniques. Nat Rev Urol. 2016;13:654-662. [PMID: 27578040] doi:10. pregnancy. 1038/nrurol.2016.154

Item 69 Answer: B Bibliography Brisbane W, Bailey MR, Sorensen MD. An overview of kidney stone imaging Educational Objective: Diagnose nephrolithiasis during techniques. Nat Rev Urol. 2016;13:654-662. [PMID: 27578040] doi:10. pregnancy. 1038/nrurol.2016.154 The most appropriate diagnostic test to perform next is kidney ultrasonography (Option B) for this pregnant patient with Item 70 Answer: C likely nephrolithiasis. Imaging is indicated for diagnosis and Educational Objective: Treat acute kidney injury due to to guide management based on stone size and location. Ultra- tumor lysis syndrome. sonography is increasingly being used as an initial diagnostic study. Although less sensitive than CT for nephrolithiasis, The most appropriate additional treatment is rasburicase particularly for detecting small stones and ureteral stones, (Option C). This young patient exhibits spontaneous tumor 155

Drewes ane Sees lysis syndrome (TLS) before the initiation of chemother- noncontrast helical CT may be able to predict the composi- apy. TLS is characterized by acute kidney injury with severe tion of the stone based on the Hounsfield units. However, CONT. hyperuricemia, hyperphosphatemia, and hypocalcemia. These this should not preempt stone analysis. Finally, noncontrast electrolyte abnormalities can lead to cardiac arrhythmias, helical CT potentially provides alternative diagnoses if neph- seizures, and death. TLS is most frequently seen in highly rolithiasis is not detected. proliferative hematologic malignancies such as acute leukemia There is no role for the use of intravenous pyelogra- and high-grade lymphomas but can develop in many other phy (IVP) (Option A) in the evaluation of kidney stones. cancers. Appropriate therapy includes prompt initiation of IVP has high sensitivity for the diagnosis of hydronephrosis isotonic volume expansion and an agent such as rasburicase. that might be caused by a stone but lacks the sensitivity Rasburicase is a urate oxidase enzyme that metabolizes urate and specificity of noncontrast helical CT in the diagnosis to allantoin, a significantly more water-soluble compound. of nephrolithiasis and potential diagnosis of stone type. Allopurinol (Option A) is the most commonly used When noncontrast helical CT is unavailable or contraindi- b urate-lowering agent. It competitively inhibits the enzyme cated, kidney ultrasonography is preferred to IVP. Finally, = “a xanthine oxidase, blocking the conversion of hypoxanthine IVP requires the use of intravenous contrast. = (a breakdown product of purines) to urate. Although allo- Kidney and bladder ultrasonography (Option B) is oO = 2) purinol will prevent new urate formation, it will not rapidly less accurate than noncontrast helical CT in the diagno- gy lower this patient’s existing serum urate level. sis of nephrolithiasis. Sensitivity ranges from 50% to 90%. = 2. Febuxostat (Option B) is a noncompetitive xanthine Small stones and stones within the ureter are frequently not (=) oe oxidase inhibitor and, as with allopurinol, blocks the forma- detected on ultrasonography. Ultrasonography is also less =. tion of urate. Febuxostat is often used in patients in whom able to determine stone size or location within the ureter. <2 J allopurinol is contraindicated. However, it is less effective However, if noncontrast CT is unavailable or if the patient @O ww than rasburicase in rapidly lowering serum urate levels. is pregnant, ultrasonography is the preferred method of The role of urinary alkalinization in TLS (Option D) evaluation. with either acetazolamide and/or sodium bicarbonate is Radiography (Option C) has little role in the evalua- unclear and controversial. Alkalinization was recommended tion of kidney stones due to poor sensitivity and specificity. to increase promote uric acid solubility. However, alkaliniza- This modality will not detect radiolucent uric acid stones tion of the urine can also promote a favorable environment and often cannot determine if the calcification visualized for precipitation of calcium phosphate. Therefore, isotonic is within or external to the urinary system. Because of low saline and rasburicase are preferred to prevent or treat TLS. cost and low amount of radiation, radiography is useful for following the movement and growth of a stone as well as monitoring total stone burden. e Tumor lysis syndrome may spontaneously occur in patients with acute leukemia or high-grade lym- phoma and is characterized by acute kidney injury e Noncontrast helical CT of the abdomen and pelvis is with severe hyperuricemia, hyperphosphatemia, and the gold standard for diagnosis of kidney stones hypocalcemia. because of its high sensitivity and specificity.

lysis syndrome (TLS) before the initiation of chemother- noncontrast helical CT may be able to predict the composi- apy. TLS is characterized by acute kidney injury with severe tion of the stone based on the Hounsfield units. However, CONT. hyperuricemia, hyperphosphatemia, and hypocalcemia. These this should not preempt stone analysis. Finally, noncontrast electrolyte abnormalities can lead to cardiac arrhythmias, helical CT potentially provides alternative diagnoses if neph- seizures, and death. TLS is most frequently seen in highly rolithiasis is not detected. proliferative hematologic malignancies such as acute leukemia There is no role for the use of intravenous pyelogra- and high-grade lymphomas but can develop in many other phy (IVP) (Option A) in the evaluation of kidney stones. cancers. Appropriate therapy includes prompt initiation of IVP has high sensitivity for the diagnosis of hydronephrosis isotonic volume expansion and an agent such as rasburicase. that might be caused by a stone but lacks the sensitivity Rasburicase is a urate oxidase enzyme that metabolizes urate and specificity of noncontrast helical CT in the diagnosis to allantoin, a significantly more water-soluble compound. of nephrolithiasis and potential diagnosis of stone type. Allopurinol (Option A) is the most commonly used When noncontrast helical CT is unavailable or contraindi- b urate-lowering agent. It competitively inhibits the enzyme cated, kidney ultrasonography is preferred to IVP. Finally, = “a xanthine oxidase, blocking the conversion of hypoxanthine IVP requires the use of intravenous contrast. = (a breakdown product of purines) to urate. Although allo- Kidney and bladder ultrasonography (Option B) is oO = 2) purinol will prevent new urate formation, it will not rapidly less accurate than noncontrast helical CT in the diagno- gy lower this patient’s existing serum urate level. sis of nephrolithiasis. Sensitivity ranges from 50% to 90%. = 2. Febuxostat (Option B) is a noncompetitive xanthine Small stones and stones within the ureter are frequently not (=) oe oxidase inhibitor and, as with allopurinol, blocks the forma- detected on ultrasonography. Ultrasonography is also less =. tion of urate. Febuxostat is often used in patients in whom able to determine stone size or location within the ureter. <2 J allopurinol is contraindicated. However, it is less effective However, if noncontrast CT is unavailable or if the patient @O ww than rasburicase in rapidly lowering serum urate levels. is pregnant, ultrasonography is the preferred method of The role of urinary alkalinization in TLS (Option D) evaluation. with either acetazolamide and/or sodium bicarbonate is Radiography (Option C) has little role in the evalua- unclear and controversial. Alkalinization was recommended tion of kidney stones due to poor sensitivity and specificity. to increase promote uric acid solubility. However, alkaliniza- This modality will not detect radiolucent uric acid stones tion of the urine can also promote a favorable environment and often cannot determine if the calcification visualized for precipitation of calcium phosphate. Therefore, isotonic is within or external to the urinary system. Because of low saline and rasburicase are preferred to prevent or treat TLS. cost and low amount of radiation, radiography is useful for following the movement and growth of a stone as well as monitoring total stone burden. e Tumor lysis syndrome may spontaneously occur in patients with acute leukemia or high-grade lym- phoma and is characterized by acute kidney injury e Noncontrast helical CT of the abdomen and pelvis is with severe hyperuricemia, hyperphosphatemia, and the gold standard for diagnosis of kidney stones hypocalcemia. because of its high sensitivity and specificity. e Treatment of tumor lysis syndrome includes prompt ¢ Ultrasonography is the preferred imaging test for sus-

lysis syndrome (TLS) before the initiation of chemother- noncontrast helical CT may be able to predict the composi- apy. TLS is characterized by acute kidney injury with severe tion of the stone based on the Hounsfield units. However, CONT. hyperuricemia, hyperphosphatemia, and hypocalcemia. These this should not preempt stone analysis. Finally, noncontrast electrolyte abnormalities can lead to cardiac arrhythmias, helical CT potentially provides alternative diagnoses if neph- seizures, and death. TLS is most frequently seen in highly rolithiasis is not detected. proliferative hematologic malignancies such as acute leukemia There is no role for the use of intravenous pyelogra- and high-grade lymphomas but can develop in many other phy (IVP) (Option A) in the evaluation of kidney stones. cancers. Appropriate therapy includes prompt initiation of IVP has high sensitivity for the diagnosis of hydronephrosis isotonic volume expansion and an agent such as rasburicase. that might be caused by a stone but lacks the sensitivity Rasburicase is a urate oxidase enzyme that metabolizes urate and specificity of noncontrast helical CT in the diagnosis to allantoin, a significantly more water-soluble compound. of nephrolithiasis and potential diagnosis of stone type. Allopurinol (Option A) is the most commonly used When noncontrast helical CT is unavailable or contraindi- b urate-lowering agent. It competitively inhibits the enzyme cated, kidney ultrasonography is preferred to IVP. Finally, = “a xanthine oxidase, blocking the conversion of hypoxanthine IVP requires the use of intravenous contrast. = (a breakdown product of purines) to urate. Although allo- Kidney and bladder ultrasonography (Option B) is oO = 2) purinol will prevent new urate formation, it will not rapidly less accurate than noncontrast helical CT in the diagno- gy lower this patient’s existing serum urate level. sis of nephrolithiasis. Sensitivity ranges from 50% to 90%. = 2. Febuxostat (Option B) is a noncompetitive xanthine Small stones and stones within the ureter are frequently not (=) oe oxidase inhibitor and, as with allopurinol, blocks the forma- detected on ultrasonography. Ultrasonography is also less =. tion of urate. Febuxostat is often used in patients in whom able to determine stone size or location within the ureter. <2 J allopurinol is contraindicated. However, it is less effective However, if noncontrast CT is unavailable or if the patient @O ww than rasburicase in rapidly lowering serum urate levels. is pregnant, ultrasonography is the preferred method of The role of urinary alkalinization in TLS (Option D) evaluation. with either acetazolamide and/or sodium bicarbonate is Radiography (Option C) has little role in the evalua- unclear and controversial. Alkalinization was recommended tion of kidney stones due to poor sensitivity and specificity. to increase promote uric acid solubility. However, alkaliniza- This modality will not detect radiolucent uric acid stones tion of the urine can also promote a favorable environment and often cannot determine if the calcification visualized for precipitation of calcium phosphate. Therefore, isotonic is within or external to the urinary system. Because of low saline and rasburicase are preferred to prevent or treat TLS. cost and low amount of radiation, radiography is useful for following the movement and growth of a stone as well as monitoring total stone burden. e Tumor lysis syndrome may spontaneously occur in patients with acute leukemia or high-grade lym- phoma and is characterized by acute kidney injury e Noncontrast helical CT of the abdomen and pelvis is with severe hyperuricemia, hyperphosphatemia, and the gold standard for diagnosis of kidney stones hypocalcemia. because of its high sensitivity and specificity. e Treatment of tumor lysis syndrome includes prompt ¢ Ultrasonography is the preferred imaging test for sus- initiation of isotonic volume expansion and rasbur- pected nephrolithiasis in pregnant women and when icase to rapidly reduce serum urate levels. CT imaging is not available.

e Treatment of tumor lysis syndrome includes prompt ¢ Ultrasonography is the preferred imaging test for sus- initiation of isotonic volume expansion and rasbur- pected nephrolithiasis in pregnant women and when icase to rapidly reduce serum urate levels. CT imaging is not available. Bibliography Bibliography Rosner MH, Perazella MA. Acute kidney injury in the patient with cancer. Mayans L. Nephrolithiasis. Prim Care. 2019;46:203-212. [PMID: 31030821] Kidney Res Clin Pract. 2019;38:295-308. [PMID: 31284363] doi:10.23876 /j. doi:10.1016/j.pop.2019.02.001 krep.19.042

Bibliography Bibliography Rosner MH, Perazella MA. Acute kidney injury in the patient with cancer. Mayans L. Nephrolithiasis. Prim Care. 2019;46:203-212. [PMID: 31030821] Kidney Res Clin Pract. 2019;38:295-308. [PMID: 31284363] doi:10.23876 /j. doi:10.1016/j.pop.2019.02.001 krep.19.042 Item 72 Answer: D Item 71 Answer: D Educational Objective: Treat metabolic acidosis in Educational Objective: Diagnose nephrolithiasis with chronic kidney disease. noncontrast helical CT. The most appropriate treatment is sodium bicarbonate The most sensitive imaging test to perform is a noncontrast supplement (Option D) for this patient with a metabolic helical abdomen and pelvis CT (Option D), which has the acidosis. There is a strong association between metabolic highest sensitivity and specificity of all imaging options used acidosis and increased progression of chronic kidney dis- in evaluating nephrolithiasis. The sensitivity of noncontrast ease (CKD) and mortality. Data suggest that repletion of helical abdominal CT for the diagnosis of nephrolithiasis bicarbonate attenuates the rate of CKD progression. Bicar- is greater than 95%. Noncontrast helical CT can also detect bonate can be given as sodium bicarbonate tablets, as a stones independent of their composition, with the excep- powder (including in the form of baking soda), or through tion of stones composed of indinavir crystals. Furthermore, a diet rich in fruit and vegetables that are endogenous 156

Aeewyer and Rettiqums alkali sources. Guidelines recommend initiation of bicar- Although diagnosis can be made by kidney biopsy, this is not bonate when the serum bicarbonate level is <22 mEq/L usually required in the setting of a good clinical and family (22 mmol/L), as seen in this patient. Bicarbonate therapy history. Genetic testing may also be used to make the diag- should be titrated to achieve a serum bicarbonate level nosis. within the normal range. Autosomal dominant tubulointerstitial kidney disease FDA black box warnings for use of erythropoietin- (Option A) should be suspected in patients with slowly stimulating agents (ESAs) (Option A) include the risk for progressive chronic kidney disease, a bland urine sediment, increased mortality and/or tumor progression in patients small kidneys, and a family history of end-stage kidney with active malignancy; increased risk for thromboembolic disease. This patient has normal-sized kidneys, microscopic events in postsurgical patients not receiving anticoagulant hematuria, and no family history of kidney dysfunction. therapy; and increased risk for serious cardiovascular events Fabry disease (Option B) follows an X-linked pattern on when ESAs are administered to patients with hemoglobin inheritance. Patients are expected to have kidney dysfunc- values >11 g/dL (110 g/L) or with a history of stroke. Because tion by adulthood alongside abnormalities in other organs n” a of the potential harm caused by ESAs in patients with CKD, such as the skin (telangiectasias and angiokeratomas), eyes, =

alkali sources. Guidelines recommend initiation of bicar- Although diagnosis can be made by kidney biopsy, this is not bonate when the serum bicarbonate level is <22 mEq/L usually required in the setting of a good clinical and family (22 mmol/L), as seen in this patient. Bicarbonate therapy history. Genetic testing may also be used to make the diag- should be titrated to achieve a serum bicarbonate level nosis. within the normal range. Autosomal dominant tubulointerstitial kidney disease FDA black box warnings for use of erythropoietin- (Option A) should be suspected in patients with slowly stimulating agents (ESAs) (Option A) include the risk for progressive chronic kidney disease, a bland urine sediment, increased mortality and/or tumor progression in patients small kidneys, and a family history of end-stage kidney with active malignancy; increased risk for thromboembolic disease. This patient has normal-sized kidneys, microscopic events in postsurgical patients not receiving anticoagulant hematuria, and no family history of kidney dysfunction. therapy; and increased risk for serious cardiovascular events Fabry disease (Option B) follows an X-linked pattern on when ESAs are administered to patients with hemoglobin inheritance. Patients are expected to have kidney dysfunc- values >11 g/dL (110 g/L) or with a history of stroke. Because tion by adulthood alongside abnormalities in other organs n” a of the potential harm caused by ESAs in patients with CKD, such as the skin (telangiectasias and angiokeratomas), eyes, = use of these agents should be restricted to patients with heart (premature coronary artery disease), brain, and/or = peripheral nervous system (severe neuropathic pain). This = hemoglobin values <10 g/dL (100 g/L) and symptoms. rs) Hemodialysis (Option B) is not an appropriate manage- patient has no kidney dysfunction or other organ abnor- sc <= ment, as this patient has stage G4 CKD. Medical management malities. co

use of these agents should be restricted to patients with heart (premature coronary artery disease), brain, and/or = peripheral nervous system (severe neuropathic pain). This = hemoglobin values <10 g/dL (100 g/L) and symptoms. rs) Hemodialysis (Option B) is not an appropriate manage- patient has no kidney dysfunction or other organ abnor- sc <= ment, as this patient has stage G4 CKD. Medical management malities. co of metabolic acidosis is indicated for these patients until Hereditary nephritis (Alport syndrome) (Option C) fol- 2) eee o progression to advanced stage G5 CKD with an estimated lows an X-linked pattern on inheritance in 85% of cases; = ~n glomerular filtration rate <10 mL/min/1.73 m2. For patients the remaining 15% of cases follow an autosomal recessive & with advanced stage G5 CKD, data indicate that there is no pattern of inheritance. In addition, hereditary nephritis is =<

o progression to advanced stage G5 CKD with an estimated lows an X-linked pattern on inheritance in 85% of cases; = ~n glomerular filtration rate <10 mL/min/1.73 m2. For patients the remaining 15% of cases follow an autosomal recessive & with advanced stage G5 CKD, data indicate that there is no pattern of inheritance. In addition, hereditary nephritis is =< mortality benefit to early initiation of renal replacement expected to have a family history of not only hematuria, therapy. The decision to start hemodialysis should be based but also proteinuria (unlike this patient), renal dysfunction upon the development of uremic symptoms refractory to (including end-stage kidney disease in most families), and medical management. both visual and hearing abnormalities. A high-protein diet (Option C) is a source of the daily acid load and would worsen rather than improve this patient’s metabolic acidosis. ¢ Thin glomerular basement membrane (GBM) disease is an autosomal dominant type IV collagen abnormal- ity that causes thinning of the GBM, resulting in e Metabolic acidosis in patients with chronic kidney hematuria but usually without proteinuria or abnor- disease should be treated with alkali therapy when mal kidney function. serum bicarbonate levels are <22 mEq/L (22 mmol/L). e Repletion of bicarbonate into the normal range in Bibliography patients with chronic kidney disease (CKD) attenuates Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen IV a345: a position paper of the Alport the rate of CKD progression. Syndrome Classification Working Group. Kidney Int. 2018;93:1045-1051. [PMID: 29551517] doi:10.1016 /j.kint.2017.12.018

mortality benefit to early initiation of renal replacement expected to have a family history of not only hematuria, therapy. The decision to start hemodialysis should be based but also proteinuria (unlike this patient), renal dysfunction upon the development of uremic symptoms refractory to (including end-stage kidney disease in most families), and medical management. both visual and hearing abnormalities. A high-protein diet (Option C) is a source of the daily acid load and would worsen rather than improve this patient’s metabolic acidosis. ¢ Thin glomerular basement membrane (GBM) disease is an autosomal dominant type IV collagen abnormal- ity that causes thinning of the GBM, resulting in e Metabolic acidosis in patients with chronic kidney hematuria but usually without proteinuria or abnor- disease should be treated with alkali therapy when mal kidney function. serum bicarbonate levels are <22 mEq/L (22 mmol/L). e Repletion of bicarbonate into the normal range in Bibliography patients with chronic kidney disease (CKD) attenuates Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen IV a345: a position paper of the Alport the rate of CKD progression. Syndrome Classification Working Group. Kidney Int. 2018;93:1045-1051. [PMID: 29551517] doi:10.1016 /j.kint.2017.12.018 Bibliography Kalantar-Zadeh K, Fouque D. Nutritional management of chronic kidney disease. N EnglJ Med. 2017;377:1765-1776. [PMID: 29091561] doi:10.1056/ Item 74 Answer: A NEJMra1700312 Educational Objective: Treat hypertension in an older patient with cardiovascular disease. Item 73 Answer: D The most appropriate management is to add chlorthalidone Educational Objective: Diagnose thin glomerular base- (Option A). Guidelines differ in recommendations for systolic ment membrane disease. blood pressure (SBP) goals in older patients. The American Thin glomerular basement membrane (GBM) disease (Option College of Cardiology/American Heart Association recom- D) is the most likely diagnosis. Also known as benign familial mend an SBP of <130 mm Hg in noninstitutionalized, ambu- hematuria, inheritance in this disease is autosomal dominant. latory community-dwelling adults 265 years of age, whereas The inherited type IV collagen abnormality causes thinning of the American College of Physicians (ACP)/American Academy the GBM, which results in hematuria but usually without pro- of Family Physicians (AAFP) recommend an SBP of <150 mm teinuria or abnormal kidney function. Thin GBM disease may Hg in most patients >60 years of age to minimize treatment- affect up to 5% of the population, with up to 50% of patients related harms. However, ACP/AAFP also recommend con- who are diagnosed reporting a family history of hematuria sidering initiating or intensifying treatment in some adults without kidney failure. Both microscopic and macroscopic >60 years of age at high cardiovascular risk to an SBP <140 mm hematuria can be seen, first manifesting in young adulthood. Hg to reduce the risk for stroke or cardiac events. Because this

Bibliography Kalantar-Zadeh K, Fouque D. Nutritional management of chronic kidney disease. N EnglJ Med. 2017;377:1765-1776. [PMID: 29091561] doi:10.1056/ Item 74 Answer: A NEJMra1700312 Educational Objective: Treat hypertension in an older patient with cardiovascular disease. Item 73 Answer: D The most appropriate management is to add chlorthalidone Educational Objective: Diagnose thin glomerular base- (Option A). Guidelines differ in recommendations for systolic ment membrane disease. blood pressure (SBP) goals in older patients. The American Thin glomerular basement membrane (GBM) disease (Option College of Cardiology/American Heart Association recom- D) is the most likely diagnosis. Also known as benign familial mend an SBP of <130 mm Hg in noninstitutionalized, ambu- hematuria, inheritance in this disease is autosomal dominant. latory community-dwelling adults 265 years of age, whereas The inherited type IV collagen abnormality causes thinning of the American College of Physicians (ACP)/American Academy the GBM, which results in hematuria but usually without pro- of Family Physicians (AAFP) recommend an SBP of <150 mm teinuria or abnormal kidney function. Thin GBM disease may Hg in most patients >60 years of age to minimize treatment- affect up to 5% of the population, with up to 50% of patients related harms. However, ACP/AAFP also recommend con- who are diagnosed reporting a family history of hematuria sidering initiating or intensifying treatment in some adults without kidney failure. Both microscopic and macroscopic >60 years of age at high cardiovascular risk to an SBP <140 mm hematuria can be seen, first manifesting in young adulthood. Hg to reduce the risk for stroke or cardiac events. Because this 157

Answers and Critiques patient with diabetes mellitus, peripheral vascular disease, testing. Anti-PLA2R antibodies are nearly 100% specific for and hyperlipidemia is at high risk for stroke or cardiac events, primary membranous nephropathy and can obviate the need initiation of a second first-line antihypertensive drug such as for kidney biopsy in patients with preserved kidney function chlorthalidone or a calcium channel blocker is reasonable. and no evidence of secondary causes as well as in patients The initiation of antihypertensive drug therapy with a with a clear contraindication to kidney biopsy. single agent followed by the addition of other agents is rea- ANCA-associated vasculitis typically presents as a rap- sonable in the very elderly or those at risk for drug interac- idly progressive glomerulonephritis characterized by a rapid tions or side effects. Guidelines recommend that the second decline in kidney function and erythrocytes and erythrocyte drug should work by a different mechanism and include a casts on urine microscopy. These findings are not present in typical first-line agent such as a calcium channel blocker, this patient; therefore, ANCA antibody testing (Option A) is thiazide diuretic, ACE inhibitor, or angiotensin receptor not appropriate. blocker (ARB); however, ACE inhibitor/ARB combinations Anti-double-stranded DNA antibodies (Option B) are > are not recommended. o-Blockers such as prazosin (Option highly specific in establishing the diagnosis of systemic —] ” B) are not used as first-line therapy for hypertension because lupus erythematosus. Although class V lupus nephritis is = they are less effective for prevention of cardiovascular dis- a cause of secondary membranous nephropathy, normal @ complement levels and negative antinuclear antibody testing ~~ n ease than other first-line agents such as thiazide diuretics. oy = Adults with hypertension and peripheral artery disease rule out lupus nephritis. Qa. (PAD) should be treated similarly to patients with hyper- Stopping anticoagulation to perform a kidney biopsy (@) ane tension without PAD. There is also no evidence that any one (Option D) in this patient with venous thromboembolism is es class of antihypertensive medication or strategy is superior. high risk; therefore, the next step in management should be —2 J Therefore, there is no indication to switch this patient from anti-PLA2R testing, which, if positive, is a definitive diagno- © rn lisinopril to ramipril (Option C). sis of membranous nephropathy. Continuing current medical therapy (Option D) may place this older patient at increased risk for cardiovascular events. Although guideline targets for SBP differ, the benefit e Serologic testing for anti-phospholipase A2 receptor

patient with diabetes mellitus, peripheral vascular disease, testing. Anti-PLA2R antibodies are nearly 100% specific for and hyperlipidemia is at high risk for stroke or cardiac events, primary membranous nephropathy and can obviate the need initiation of a second first-line antihypertensive drug such as for kidney biopsy in patients with preserved kidney function chlorthalidone or a calcium channel blocker is reasonable. and no evidence of secondary causes as well as in patients The initiation of antihypertensive drug therapy with a with a clear contraindication to kidney biopsy. single agent followed by the addition of other agents is rea- ANCA-associated vasculitis typically presents as a rap- sonable in the very elderly or those at risk for drug interac- idly progressive glomerulonephritis characterized by a rapid tions or side effects. Guidelines recommend that the second decline in kidney function and erythrocytes and erythrocyte drug should work by a different mechanism and include a casts on urine microscopy. These findings are not present in typical first-line agent such as a calcium channel blocker, this patient; therefore, ANCA antibody testing (Option A) is thiazide diuretic, ACE inhibitor, or angiotensin receptor not appropriate. blocker (ARB); however, ACE inhibitor/ARB combinations Anti-double-stranded DNA antibodies (Option B) are > are not recommended. o-Blockers such as prazosin (Option highly specific in establishing the diagnosis of systemic —] ” B) are not used as first-line therapy for hypertension because lupus erythematosus. Although class V lupus nephritis is = they are less effective for prevention of cardiovascular dis- a cause of secondary membranous nephropathy, normal @ complement levels and negative antinuclear antibody testing ~~ n ease than other first-line agents such as thiazide diuretics. oy = Adults with hypertension and peripheral artery disease rule out lupus nephritis. Qa. (PAD) should be treated similarly to patients with hyper- Stopping anticoagulation to perform a kidney biopsy (@) ane tension without PAD. There is also no evidence that any one (Option D) in this patient with venous thromboembolism is es class of antihypertensive medication or strategy is superior. high risk; therefore, the next step in management should be —2 J Therefore, there is no indication to switch this patient from anti-PLA2R testing, which, if positive, is a definitive diagno- © rn lisinopril to ramipril (Option C). sis of membranous nephropathy. Continuing current medical therapy (Option D) may place this older patient at increased risk for cardiovascular events. Although guideline targets for SBP differ, the benefit e Serologic testing for anti-phospholipase A2 receptor of SBP reduction to <130-140 mm Hg in older patients at antibodies is a noninvasive test that approaches 100% increased risk for stroke or cardiovascular events is likely to specificity for primary membranous nephropathy. exceed harms. e Serologic testing for anti-phospholipase A2 receptor antibodies can eliminate the need for kidney biopsy in patients with preserved kidney function and no e Although guidelines differ in recommendations for evidence of secondary causes as well as in patients systolic blood pressure (SBP) targets, the benefit of with a clear contraindication to kidney biopsy. SBP reduction to <130-140 mm Hg in older patients at increased risk for stroke or cardiovascular events is Bibliography likely to exceed harms. Bobart SA, De Vriese AS, Pawar AS, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Bibliography Kidney Int. 2019;95:429-38. [PMID: 30665573] doi:10.1016/j.kint. 2018.10.021 Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. [PMID: 31060074] doi:10.7326/AITC201905070

of SBP reduction to <130-140 mm Hg in older patients at antibodies is a noninvasive test that approaches 100% increased risk for stroke or cardiovascular events is likely to specificity for primary membranous nephropathy. exceed harms. e Serologic testing for anti-phospholipase A2 receptor antibodies can eliminate the need for kidney biopsy in patients with preserved kidney function and no e Although guidelines differ in recommendations for evidence of secondary causes as well as in patients systolic blood pressure (SBP) targets, the benefit of with a clear contraindication to kidney biopsy. SBP reduction to <130-140 mm Hg in older patients at increased risk for stroke or cardiovascular events is Bibliography likely to exceed harms. Bobart SA, De Vriese AS, Pawar AS, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Bibliography Kidney Int. 2019;95:429-38. [PMID: 30665573] doi:10.1016/j.kint. 2018.10.021 Byrd JB, Brook RD. Hypertension. Ann Intern Med. 2019;170:ITC65-ITC80. [PMID: 31060074] doi:10.7326/AITC201905070 Item 76 Answer: A Item 75 Answer: C Educational Objective: Recognize chronic kidney disease Educational Objective: Diagnose membranous as an independent risk factor for cardiovascular disease. nephropathy using noninvasive testing. The most likely expected cause of premature death in this Anti-phospholipase A2 receptor (PLA2R) antibody (Option patient is cardiovascular disease (Option A). Patients with C) testing is the most appropriate diagnostic test to perform stage G3 chronic kidney disease (CKD) are more likely to die next. This patient with the nephrotic syndrome and venous of a cardiovascular event than they are to progress to stage thromboembolism most likely has membranous nephropa- G4 CKD or to end-stage kidney disease (ESKD) that requires thy. Patients with membranous nephropathy are particularly initiation of renal replacement therapy. Also, the risk for car- prone to thrombotic complications. These clots include lower diovascular-related death in patients with stages G3 and G4 extremity, pulmonary, and renal vein thromboses; they can CKD is four to five times higher than the risk for progression occur in up to 25% of patients and are most likely to occur to ESKD (Option B). CKD and albuminuria are both inde- within the first 6 months of diagnosis. The risk for clotting pendent risk factors for cardiovascular disease. Mortality risk increases when serum albumin is <2.8 g/dL (28 g/L) and in these patients increases with a decreasing estimated glo- increases proportionally with decreasing serum albumin lev- merular filtration rate and increasing albuminuria. Therefore, els. The diagnosis of primary membranous nephropathy can management of CKD addresses traditional cardiovascular risk be made noninvasively using serum anti-PLA2R antibody factors, such as blood pressure control, glycemic control for

Item 76 Answer: A Item 75 Answer: C Educational Objective: Recognize chronic kidney disease Educational Objective: Diagnose membranous as an independent risk factor for cardiovascular disease. nephropathy using noninvasive testing. The most likely expected cause of premature death in this Anti-phospholipase A2 receptor (PLA2R) antibody (Option patient is cardiovascular disease (Option A). Patients with C) testing is the most appropriate diagnostic test to perform stage G3 chronic kidney disease (CKD) are more likely to die next. This patient with the nephrotic syndrome and venous of a cardiovascular event than they are to progress to stage thromboembolism most likely has membranous nephropa- G4 CKD or to end-stage kidney disease (ESKD) that requires thy. Patients with membranous nephropathy are particularly initiation of renal replacement therapy. Also, the risk for car- prone to thrombotic complications. These clots include lower diovascular-related death in patients with stages G3 and G4 extremity, pulmonary, and renal vein thromboses; they can CKD is four to five times higher than the risk for progression occur in up to 25% of patients and are most likely to occur to ESKD (Option B). CKD and albuminuria are both inde- within the first 6 months of diagnosis. The risk for clotting pendent risk factors for cardiovascular disease. Mortality risk increases when serum albumin is <2.8 g/dL (28 g/L) and in these patients increases with a decreasing estimated glo- increases proportionally with decreasing serum albumin lev- merular filtration rate and increasing albuminuria. Therefore, els. The diagnosis of primary membranous nephropathy can management of CKD addresses traditional cardiovascular risk be made noninvasively using serum anti-PLA2R antibody factors, such as blood pressure control, glycemic control for 158

patients with diabetes mellitus, and treatment of hyperlip- urine dipstick is positive for blood in the absence of erythro- idemia. cytes. Other urinary findings include pigmented granular casts Infection is the second leading cause of death in ESKD and hemoglobinuria. Both myoglobinuria and hemoglobin- (Option C). Patients are at increased risk due to a relatively uria can cause tea-colored urine and urine dipstick positive immunosuppressed state from chronic inflammation and for blood; however, hemoglobin produces a reddish-brown frequent exposure to the health care environment, including color in centrifuged serum and myoglobin does not discolor long-term need for vascular access and related-risk of bacte- the serum. The treatment is expansion of the intravascular remia and sepsis. Infecting organisms are usually common volume with 0.9% saline. organisms such as Staphylococcus aureus acquired through Although primaquine is a newly initiated medica- hemodialysis. tion, the short time course and absence of pyuria are not Acquired cystic kidney disease becomes more common consistent with drug-induced acute interstitial nephritis and progresses during the course of ESKD, and some studies (Option A). suggest that it may affect >50% of patients who have had In this patient, the presence of a urine dipstick positive 2) cf} ESKD for >3 years. The epithelial cells lining these cysts may for blood in the absence of erythrocytes and numerous s x undergo malignant transformation by poorly understood pigmented granular casts supports the diagnosis of heme = = mechanisms. Patients with ESKD have a markedly increased pigment nephropathy rather than prerenal AKI (Option C), cw) risk for renal cell carcinoma (Option D); however, malig- which is associated with a benign urinalysis. Ee = nancy is only the third leading cause of death in patients When exposed to an oxidative stress, patients with © wn with ESKD, and renal cell carcinoma comprises only a por- G6PD deficiency can develop acute hemolytic anemia. i o tion of malignancy-related deaths. Routine screening is not Rhabdomyolysis (Option D) is not part of the clinical syn- = wn recommended, but a high level of suspicion is warranted in drome. However, the clinical course of rhabdomyolysis is e similar to that of pigment nephropathy due to hemolysis. = patients with symptoms such as new-onset gross hematuria or unexplained flank pain. Laboratory findings of rhabdomyolysis-induced AKI] include hyperkalemia, hyperphosphatemia, hyperuricemia, hypo- calcemia, metabolic acidosis, elevated serum creatinine, and ¢ Cardiovascular disease is the leading cause of death elevated muscle enzymes such as serum creatine kinase among patients with chronic kidney disease, and (typically >5000 U/L), lactate dehydrogenase, and aspartate management should address cardiovascular risk fac- and alanine aminotransferases. tors, such as blood pressure control, glycemic control, and treatment of hyperlipidemia. ¢ Myoglobin and hemoglobin are heme pigment-containing

patients with diabetes mellitus, and treatment of hyperlip- urine dipstick is positive for blood in the absence of erythro- idemia. cytes. Other urinary findings include pigmented granular casts Infection is the second leading cause of death in ESKD and hemoglobinuria. Both myoglobinuria and hemoglobin- (Option C). Patients are at increased risk due to a relatively uria can cause tea-colored urine and urine dipstick positive immunosuppressed state from chronic inflammation and for blood; however, hemoglobin produces a reddish-brown frequent exposure to the health care environment, including color in centrifuged serum and myoglobin does not discolor long-term need for vascular access and related-risk of bacte- the serum. The treatment is expansion of the intravascular remia and sepsis. Infecting organisms are usually common volume with 0.9% saline. organisms such as Staphylococcus aureus acquired through Although primaquine is a newly initiated medica- hemodialysis. tion, the short time course and absence of pyuria are not Acquired cystic kidney disease becomes more common consistent with drug-induced acute interstitial nephritis and progresses during the course of ESKD, and some studies (Option A). suggest that it may affect >50% of patients who have had In this patient, the presence of a urine dipstick positive 2) cf} ESKD for >3 years. The epithelial cells lining these cysts may for blood in the absence of erythrocytes and numerous s x undergo malignant transformation by poorly understood pigmented granular casts supports the diagnosis of heme = = mechanisms. Patients with ESKD have a markedly increased pigment nephropathy rather than prerenal AKI (Option C), cw) risk for renal cell carcinoma (Option D); however, malig- which is associated with a benign urinalysis. Ee = nancy is only the third leading cause of death in patients When exposed to an oxidative stress, patients with © wn with ESKD, and renal cell carcinoma comprises only a por- G6PD deficiency can develop acute hemolytic anemia. i o tion of malignancy-related deaths. Routine screening is not Rhabdomyolysis (Option D) is not part of the clinical syn- = wn recommended, but a high level of suspicion is warranted in drome. However, the clinical course of rhabdomyolysis is e similar to that of pigment nephropathy due to hemolysis. = patients with symptoms such as new-onset gross hematuria or unexplained flank pain. Laboratory findings of rhabdomyolysis-induced AKI] include hyperkalemia, hyperphosphatemia, hyperuricemia, hypo- calcemia, metabolic acidosis, elevated serum creatinine, and ¢ Cardiovascular disease is the leading cause of death elevated muscle enzymes such as serum creatine kinase among patients with chronic kidney disease, and (typically >5000 U/L), lactate dehydrogenase, and aspartate management should address cardiovascular risk fac- and alanine aminotransferases. tors, such as blood pressure control, glycemic control, and treatment of hyperlipidemia. ¢ Myoglobin and hemoglobin are heme pigment-containing Bibliography proteins that can cause acute kidney injury.

patients with diabetes mellitus, and treatment of hyperlip- urine dipstick is positive for blood in the absence of erythro- idemia. cytes. Other urinary findings include pigmented granular casts Infection is the second leading cause of death in ESKD and hemoglobinuria. Both myoglobinuria and hemoglobin- (Option C). Patients are at increased risk due to a relatively uria can cause tea-colored urine and urine dipstick positive immunosuppressed state from chronic inflammation and for blood; however, hemoglobin produces a reddish-brown frequent exposure to the health care environment, including color in centrifuged serum and myoglobin does not discolor long-term need for vascular access and related-risk of bacte- the serum. The treatment is expansion of the intravascular remia and sepsis. Infecting organisms are usually common volume with 0.9% saline. organisms such as Staphylococcus aureus acquired through Although primaquine is a newly initiated medica- hemodialysis. tion, the short time course and absence of pyuria are not Acquired cystic kidney disease becomes more common consistent with drug-induced acute interstitial nephritis and progresses during the course of ESKD, and some studies (Option A). suggest that it may affect >50% of patients who have had In this patient, the presence of a urine dipstick positive 2) cf} ESKD for >3 years. The epithelial cells lining these cysts may for blood in the absence of erythrocytes and numerous s x undergo malignant transformation by poorly understood pigmented granular casts supports the diagnosis of heme = = mechanisms. Patients with ESKD have a markedly increased pigment nephropathy rather than prerenal AKI (Option C), cw) risk for renal cell carcinoma (Option D); however, malig- which is associated with a benign urinalysis. Ee = nancy is only the third leading cause of death in patients When exposed to an oxidative stress, patients with © wn with ESKD, and renal cell carcinoma comprises only a por- G6PD deficiency can develop acute hemolytic anemia. i o tion of malignancy-related deaths. Routine screening is not Rhabdomyolysis (Option D) is not part of the clinical syn- = wn recommended, but a high level of suspicion is warranted in drome. However, the clinical course of rhabdomyolysis is e similar to that of pigment nephropathy due to hemolysis. = patients with symptoms such as new-onset gross hematuria or unexplained flank pain. Laboratory findings of rhabdomyolysis-induced AKI] include hyperkalemia, hyperphosphatemia, hyperuricemia, hypo- calcemia, metabolic acidosis, elevated serum creatinine, and ¢ Cardiovascular disease is the leading cause of death elevated muscle enzymes such as serum creatine kinase among patients with chronic kidney disease, and (typically >5000 U/L), lactate dehydrogenase, and aspartate management should address cardiovascular risk fac- and alanine aminotransferases. tors, such as blood pressure control, glycemic control, and treatment of hyperlipidemia. ¢ Myoglobin and hemoglobin are heme pigment-containing Bibliography proteins that can cause acute kidney injury. Coresh J, Turin TC, Matsushita K, et al. Decline in estimated glomerular fil- ¢ Heme pigment nephropathy is associated with a posi- tration rate and subsequent risk of end-stage renal disease and mortality. JAMA. 2014;311:2518-2531. [PMID: 24892770] tive urine dipstick for blood in the absence of erythro- cytes and the presence of pigmented granular casts.

Coresh J, Turin TC, Matsushita K, et al. Decline in estimated glomerular fil- ¢ Heme pigment nephropathy is associated with a posi- tration rate and subsequent risk of end-stage renal disease and mortality. JAMA. 2014;311:2518-2531. [PMID: 24892770] tive urine dipstick for blood in the absence of erythro- cytes and the presence of pigmented granular casts. Item 77 Answer: B Bibliography Kirsch AH, Pollheimer MJ, Troppan K, Horina JH, Rosenkranz AR, Eller K. Educational Objective: Diagnose heme pigment The Case | Acute kidney injury and hemolysis in a 58-year-old woman. nephropathy. Kidney Int. 2017;91(4):993-994. [PMID: 28314587] doi:10.1016/j.kint. 2016.09.008 The most likely diagnosis is heme pigment nephropathy (Option B). This patient likely has underlying glucose-6- phosphate dehydrogenase (G6PD) deficiency, and acute hemo- Item 78 Answer: A lytic anemia due to primaquine exposure. Primaquine can Educational Objective: Identify ferric carboxymaltose precipitate hemolytic anemia in such patients, as can other as the cause of hypophosphatemia. antimalarial agents, rasburicase, sulfonamides (e.g., sulfame- thoxazole), some nonsulfa antibiotics (e.g., isoniazid), dap- The most likely cause of this patient’s hypophosphatemia sone, and nitrofurantoin. Myoglobin and hemoglobin are heme is ferric carboxymaltose (Option A). This parenteral iron pigment-containing proteins that can cause acute kidney solution can be administered in a single dose and thus has injury (AKI). Heme pigment nephropathy occurs when large been increasingly used to treat individuals with severe iron amounts of heme pigment are released into the circulation deficiency that cannot be corrected with oral preparations. due to massive intravascular hemolysis. Pigment nephropathy However, this medication can result in transient hypophos- can cause acute tubular necrosis as the result of volume deple- phatemia. Although most reported cases occur after a patient tion, renal vasoconstriction, direct heme protein-mediated receives repeated doses, hypophosphatemia has occurred cytotoxicity, and intraluminal cast formation. Laboratory find- after a single dose. The decrease in serum phosphorus is ings include anemia, increased serum lactate dehydrogenase, typically not significant, but for patients with risk factors decreased haptoglobin, and increased serum creatinine. The (e.g., vitamin D deficiency, malnutrition, gastrointestinal

Item 77 Answer: B Bibliography Kirsch AH, Pollheimer MJ, Troppan K, Horina JH, Rosenkranz AR, Eller K. Educational Objective: Diagnose heme pigment The Case | Acute kidney injury and hemolysis in a 58-year-old woman. nephropathy. Kidney Int. 2017;91(4):993-994. [PMID: 28314587] doi:10.1016/j.kint. 2016.09.008 The most likely diagnosis is heme pigment nephropathy (Option B). This patient likely has underlying glucose-6- phosphate dehydrogenase (G6PD) deficiency, and acute hemo- Item 78 Answer: A lytic anemia due to primaquine exposure. Primaquine can Educational Objective: Identify ferric carboxymaltose precipitate hemolytic anemia in such patients, as can other as the cause of hypophosphatemia. antimalarial agents, rasburicase, sulfonamides (e.g., sulfame- thoxazole), some nonsulfa antibiotics (e.g., isoniazid), dap- The most likely cause of this patient’s hypophosphatemia sone, and nitrofurantoin. Myoglobin and hemoglobin are heme is ferric carboxymaltose (Option A). This parenteral iron pigment-containing proteins that can cause acute kidney solution can be administered in a single dose and thus has injury (AKI). Heme pigment nephropathy occurs when large been increasingly used to treat individuals with severe iron amounts of heme pigment are released into the circulation deficiency that cannot be corrected with oral preparations. due to massive intravascular hemolysis. Pigment nephropathy However, this medication can result in transient hypophos- can cause acute tubular necrosis as the result of volume deple- phatemia. Although most reported cases occur after a patient tion, renal vasoconstriction, direct heme protein-mediated receives repeated doses, hypophosphatemia has occurred cytotoxicity, and intraluminal cast formation. Laboratory find- after a single dose. The decrease in serum phosphorus is ings include anemia, increased serum lactate dehydrogenase, typically not significant, but for patients with risk factors decreased haptoglobin, and increased serum creatinine. The (e.g., vitamin D deficiency, malnutrition, gastrointestinal 159

Answers and Critiques disease, or use of medications that bind phosphorus in the common cause of secondary hypertension in middle-aged gut), severe symptomatic hypophosphatemia has occurred. adults and an important cause of resistant hypertension. The mechanism has shown to be secondary to increases in In this patient, a dedicated adrenal CT scan shows diffuse fibroblast growth factor 23 (FGF-23), which cause phospha- bilateral adrenal hyperplasia, as seen in two thirds of patients turia and a decrease in 1-hydroxylation of vitamin D. Other with primary hyperaldosteronism. Diffuse bilateral hyper- causes of hypophosphatemia include hungry bone syndrome plasia is managed by an aldosterone receptor antagonist such following parathyroidectomy; refeeding of starved individ- as eplerenone. uals; oncogenic osteomalacia associated with sarcomas that Bilateral adrenal vein sampling (Option A) for aldoste- secrete FGF-23; and X-linked hypophosphatemic rickets due rone is used to distinguish between unilateral adenoma and to a mutation that causes increased FGF-23. It can also occur bilateral hyperplasia in patients who are surgical candidates following liver resection in a living liver donor. and would like to pursue surgical management. Functioning A low phosphorus diet (Option B) is not the cause of adrenal adenomas can be very small and may not be detected > this patient’s hypophosphatemia. The kidney can reduce with advanced imaging, but they can be implicated as a cause P= n phosphorus excretion to very low levels, but only a severely of primary hyperaldosteronism if aldosterone secretion later- = phosphate-restricted diet will decrease the serum phos- alizes to one gland. This patient has multiple comorbid con- © phorus levels (significantly more frequently in women). In ditions and does not want to pursue any surgical procedures. = 7.)

disease, or use of medications that bind phosphorus in the common cause of secondary hypertension in middle-aged gut), severe symptomatic hypophosphatemia has occurred. adults and an important cause of resistant hypertension. The mechanism has shown to be secondary to increases in In this patient, a dedicated adrenal CT scan shows diffuse fibroblast growth factor 23 (FGF-23), which cause phospha- bilateral adrenal hyperplasia, as seen in two thirds of patients turia and a decrease in 1-hydroxylation of vitamin D. Other with primary hyperaldosteronism. Diffuse bilateral hyper- causes of hypophosphatemia include hungry bone syndrome plasia is managed by an aldosterone receptor antagonist such following parathyroidectomy; refeeding of starved individ- as eplerenone. uals; oncogenic osteomalacia associated with sarcomas that Bilateral adrenal vein sampling (Option A) for aldoste- secrete FGF-23; and X-linked hypophosphatemic rickets due rone is used to distinguish between unilateral adenoma and to a mutation that causes increased FGF-23. It can also occur bilateral hyperplasia in patients who are surgical candidates following liver resection in a living liver donor. and would like to pursue surgical management. Functioning A low phosphorus diet (Option B) is not the cause of adrenal adenomas can be very small and may not be detected > this patient’s hypophosphatemia. The kidney can reduce with advanced imaging, but they can be implicated as a cause P= n phosphorus excretion to very low levels, but only a severely of primary hyperaldosteronism if aldosterone secretion later- = phosphate-restricted diet will decrease the serum phos- alizes to one gland. This patient has multiple comorbid con- © phorus levels (significantly more frequently in women). In ditions and does not want to pursue any surgical procedures. = 7.) is") addition, the high fractional excretion of phosphorus iden- Therefore, adrenal vein sampling is not indicated. s 2. tifies renal wasting of phosphorus and excludes poor dietary An MRI of the adrenal glands (Option C) is not indicated (=) = intake as the cause of her hypophosphatemia. because CT of the adrenal glands, which was already per- = This patient’s serum bicarbonate level is low, suggesting formed, has superior spatial resolution compared with MRI mad = either metabolic acidosis (Option C) or compensation for respi- for the assessment of adrenal glands. @ w“ ratory alkalosis. Because there is no evidence of an increased In most patients, the diagnosis of primary hyperaldoste- respiratory rate, the low serum bicarbonate level most likely ronism is confirmed by additional testing following a positive represents a metabolic acidosis. Although metabolic acidosis screening test. The oral sodium loading test is performed to and respiratory alkalosis can shift phosphorus into cells, met- detect autonomous aldosterone secretion following sodium abolic acidosis has a minimal effect and thus would not be the chloride loading, either orally or by intravenous infusion. How- cause of this patient’s hypophosphatemia. Additionally, the ele- ever, this confirmatory test is only performed after the patient’s vated fractional excretion of phosphorus eliminates intracellu- blood pressure is controlled and hypokalemia corrected. lar shift of phosphorus as the cause of her hypophosphatemia. Although oral sodium loading (Option D) is a possible confir- Although prednisone (Option D) can cause muscle matory test, it should not be initiated in this patient at this time. breakdown and interfere with vitamin D metabolism, it does not typically cause hypophosphatemia. e Primary hyperaldosteronism is the most common cause of secondary hypertension in middle-aged e Ferric carboxymaltose, an intravenous iron prepara- adults and an important cause of resistant hyper- tion, has been associated with hypophosphatemia by tension. causing renal phosphate wasting. e Primary hyperaldosteronism is most commonly caused by bilateral adrenal hyperplasia and is man- Bibliography aged by an aldosterone receptor antagonist. Ifie E, Oyibo SO, Joshi H, et al. Symptomatic hypophosphataemia after intravenous iron therapy: an underrated adverse reaction. Endocrinol Diabetes Metab Case Rep. 2019;2019. [PMID: 31385673] doi:10.1530/ Bibliography EDM-19-0065 Funder JW, Carey RM, Mantero F, et al. The management of primary aldo- steronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101: Item 79 Answer: B 1889-1916. [PMID: 26934393] doi:10.1210/jc.2015-4061

is") addition, the high fractional excretion of phosphorus iden- Therefore, adrenal vein sampling is not indicated. s 2. tifies renal wasting of phosphorus and excludes poor dietary An MRI of the adrenal glands (Option C) is not indicated (=) = intake as the cause of her hypophosphatemia. because CT of the adrenal glands, which was already per- = This patient’s serum bicarbonate level is low, suggesting formed, has superior spatial resolution compared with MRI mad = either metabolic acidosis (Option C) or compensation for respi- for the assessment of adrenal glands. @ w“ ratory alkalosis. Because there is no evidence of an increased In most patients, the diagnosis of primary hyperaldoste- respiratory rate, the low serum bicarbonate level most likely ronism is confirmed by additional testing following a positive represents a metabolic acidosis. Although metabolic acidosis screening test. The oral sodium loading test is performed to and respiratory alkalosis can shift phosphorus into cells, met- detect autonomous aldosterone secretion following sodium abolic acidosis has a minimal effect and thus would not be the chloride loading, either orally or by intravenous infusion. How- cause of this patient’s hypophosphatemia. Additionally, the ele- ever, this confirmatory test is only performed after the patient’s vated fractional excretion of phosphorus eliminates intracellu- blood pressure is controlled and hypokalemia corrected. lar shift of phosphorus as the cause of her hypophosphatemia. Although oral sodium loading (Option D) is a possible confir- Although prednisone (Option D) can cause muscle matory test, it should not be initiated in this patient at this time. breakdown and interfere with vitamin D metabolism, it does not typically cause hypophosphatemia. e Primary hyperaldosteronism is the most common cause of secondary hypertension in middle-aged e Ferric carboxymaltose, an intravenous iron prepara- adults and an important cause of resistant hyper- tion, has been associated with hypophosphatemia by tension. causing renal phosphate wasting. e Primary hyperaldosteronism is most commonly caused by bilateral adrenal hyperplasia and is man- Bibliography aged by an aldosterone receptor antagonist. Ifie E, Oyibo SO, Joshi H, et al. Symptomatic hypophosphataemia after intravenous iron therapy: an underrated adverse reaction. Endocrinol Diabetes Metab Case Rep. 2019;2019. [PMID: 31385673] doi:10.1530/ Bibliography EDM-19-0065 Funder JW, Carey RM, Mantero F, et al. The management of primary aldo- steronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101: Item 79 Answer: B 1889-1916. [PMID: 26934393] doi:10.1210/jc.2015-4061 Educational Objective: Treat primary hyperaldostero- nism. Item 80 Answer: B Initiating eplerenone therapy (Option B) is the most appro- Educational Objective: Diagnose a mixed acid-base priate next step in management. This patient with resistant disorder. hypertension was evaluated for secondary causes of hyper- tension. A plasma aldosterone concentration/plasma renin The most likely acid-base disorder is a respiratory alkalosis activity ratio >20 with a plasma aldosterone concentration of and normal gap metabolic acidosis (Option B). The first step at least 15 ng/dL (414 pmol/L) is considered a positive result in the interpretation of acid-base disorders usually requires for primary aldosteronism and patients should be referred to the identification of the likely dominant or primary acid-base an endocrinologist or nephrologist, who may perform addi- disorder, followed by an assessment of the compensatory tional testing to confirm inappropriate aldosterone secretion response. When measured values fall outside the expected ina salt-replete state. Primary hyperaldosteronism is the most compensatory range, a mixed acid-base disorder is considered

Educational Objective: Treat primary hyperaldostero- nism. Item 80 Answer: B Initiating eplerenone therapy (Option B) is the most appro- Educational Objective: Diagnose a mixed acid-base priate next step in management. This patient with resistant disorder. hypertension was evaluated for secondary causes of hyper- tension. A plasma aldosterone concentration/plasma renin The most likely acid-base disorder is a respiratory alkalosis activity ratio >20 with a plasma aldosterone concentration of and normal gap metabolic acidosis (Option B). The first step at least 15 ng/dL (414 pmol/L) is considered a positive result in the interpretation of acid-base disorders usually requires for primary aldosteronism and patients should be referred to the identification of the likely dominant or primary acid-base an endocrinologist or nephrologist, who may perform addi- disorder, followed by an assessment of the compensatory tional testing to confirm inappropriate aldosterone secretion response. When measured values fall outside the expected ina salt-replete state. Primary hyperaldosteronism is the most compensatory range, a mixed acid-base disorder is considered 160

Answers and Critiques present. The primary disorder is usually reflected by the blood viral load measurement and genotyping. This patient’s clin- pH. Appropriate compensation may result in near-normal pH ical presentation (purpuric rash) and laboratory results (low CONT. but never a normal pH. In patients with an obvious acid-base complement levels, positive rheumatoid factor, and positive disturbance (for example, an abnormal serum bicarbonate), a cryoglobulins) support the diagnosis of cryoglobulinemic glo- normal pH suggests the presence of a mixed acid-base disorder. merulonephritis; biopsy is most likely to reveal membranop- In this case, the patient’s pH of 7.4 does not allow for a clear roliferative glomerulonephritis (MPGN). Cryoglobulinemia assignment of the primary disorder and therefore indicates denotes the presence of clonal or polyclonal immunoglob- a mixed acid-base disorder. The patient has a Pco, of 27 mm ulins that precipitate in the serum at temperatures <37.0 °C Hg (3.6 kPa), suggesting the presence of a respiratory alkalo- (98.6 °F) and dissolve with rewarming. Cryoglobulinemia is sis. The expected metabolic compensation for chronic respi- classified as type I, II, or III based on the composition of the ratory alkalosis is a reduction in the serum bicarbonate of 4 to cryoglobulins. Type I cryoglobulinemia involves a monoclonal 5 mEq/L (4-5 mmol/L) for each 10 mm Hg (1.3 kPa) decrease immunoglobulin, usually IgM, and is associated with plasma in the Pco,. In this case, the decrease in Pco, is 13 mm Hg cell dyscrasias. Types II and III are called mixed cryoglobulin- rv) bs) (1.7 kPa); thus, the serum bicarbonate is expected to be 5.2 to emia; they are composed of a mixture of polyclonal IgG and =

present. The primary disorder is usually reflected by the blood viral load measurement and genotyping. This patient’s clin- pH. Appropriate compensation may result in near-normal pH ical presentation (purpuric rash) and laboratory results (low CONT. but never a normal pH. In patients with an obvious acid-base complement levels, positive rheumatoid factor, and positive disturbance (for example, an abnormal serum bicarbonate), a cryoglobulins) support the diagnosis of cryoglobulinemic glo- normal pH suggests the presence of a mixed acid-base disorder. merulonephritis; biopsy is most likely to reveal membranop- In this case, the patient’s pH of 7.4 does not allow for a clear roliferative glomerulonephritis (MPGN). Cryoglobulinemia assignment of the primary disorder and therefore indicates denotes the presence of clonal or polyclonal immunoglob- a mixed acid-base disorder. The patient has a Pco, of 27 mm ulins that precipitate in the serum at temperatures <37.0 °C Hg (3.6 kPa), suggesting the presence of a respiratory alkalo- (98.6 °F) and dissolve with rewarming. Cryoglobulinemia is sis. The expected metabolic compensation for chronic respi- classified as type I, II, or III based on the composition of the ratory alkalosis is a reduction in the serum bicarbonate of 4 to cryoglobulins. Type I cryoglobulinemia involves a monoclonal 5 mEq/L (4-5 mmol/L) for each 10 mm Hg (1.3 kPa) decrease immunoglobulin, usually IgM, and is associated with plasma in the Pco,. In this case, the decrease in Pco, is 13 mm Hg cell dyscrasias. Types II and III are called mixed cryoglobulin- rv) bs) (1.7 kPa); thus, the serum bicarbonate is expected to be 5.2 to emia; they are composed of a mixture of polyclonal IgG and = 6.5 mEq/L (5.2-6.5 mmol/L) lower than normal. Therefore, monoclonal or polyclonal IgM. Mixed cryoglobulinemia is = expected serum bicarbonate would be calculated as follows: usually seen in association with infections such as HCV, con- = 1S) Normal Bicarbonate - Expected Compensation nective disorders, and, rarely, lymphoproliferative disorders. s = 24 - (5.2-6.5) mEq/L (mmol/L) = 17.5-18.8 mEq/L Cutaneous symptoms (palpable purpura, Raynaud phenom- c

6.5 mEq/L (5.2-6.5 mmol/L) lower than normal. Therefore, monoclonal or polyclonal IgM. Mixed cryoglobulinemia is = expected serum bicarbonate would be calculated as follows: usually seen in association with infections such as HCV, con- = 1S) Normal Bicarbonate - Expected Compensation nective disorders, and, rarely, lymphoproliferative disorders. s = 24 - (5.2-6.5) mEq/L (mmol/L) = 17.5-18.8 mEq/L Cutaneous symptoms (palpable purpura, Raynaud phenom- c (17.5-18.8 mmol/L) enon, ulcers, necrosis, and livedo reticularis) predominate in ) be bc) 70% to 90% of patients with mixed cryoglobulinemia. Periph- The patient’s serum bicarbonate of 16 mEq/L (16 mmol/L) = eral neuropathy (60%), arthritis (40%), and glomerulonephri- wn is lower than expected, indicating the presence of a concur [= tis (40%) are common. An estimated 2% to 3% of the world <= rent metabolic acidosis. The anion gap of 7 is normal, indi- population has HCV, but higher prevalence rates are seen in cating a normal anion gap metabolic acidosis. certain geographic locations, such as Egypt, where >10% of the Respiratory alkalosis with an increased anion gap met population has HCV. Treatment of cryoglobulinemic glomeru- abolic acidosis (Option A) is not correct because the anion lonephritis due to HCV infection is aimed at eradication of the gap is 7, and thus not exceeding the normal threshold of 8.0 virus using direct-acting antiviral drugs with or without con- to 10 mEq/L + 2.0 mEq/L (8.0-10 mmol/L + 2.0 mmol/L). comitant immunosuppression based on severity of disease. Respiratory alkalosis, normal anion gap metabolic Hepatitis A virus (Option B) infection has not been acidosis, and metabolic alkalosis (Option C) is not correct associated with specific glomerular lesions. Although hep- because the serum bicarbonate is lower, not higher, than the atitis B virus (HBV) infection and HIV infection (Options expected compensatory response. A, C) have been linked to glomerular diseases, these have Respiratory alkalosis with chronic compensation (Option classically been nephrotic syndromes, specifically membra- D) is partially correct but does not account for the serum nous nephropathy with HBV and focal segmental glomeru- bicarbonate level being lower than the expected compensatory losclerosis with HIV. This patient has a nephritic syndrome response, which indicates a concurrent metabolic acidosis. not compatible with HBV- or HIV-associated glomerular diseases.

(17.5-18.8 mmol/L) enon, ulcers, necrosis, and livedo reticularis) predominate in ) be bc) 70% to 90% of patients with mixed cryoglobulinemia. Periph- The patient’s serum bicarbonate of 16 mEq/L (16 mmol/L) = eral neuropathy (60%), arthritis (40%), and glomerulonephri- wn is lower than expected, indicating the presence of a concur [= tis (40%) are common. An estimated 2% to 3% of the world <= rent metabolic acidosis. The anion gap of 7 is normal, indi- population has HCV, but higher prevalence rates are seen in cating a normal anion gap metabolic acidosis. certain geographic locations, such as Egypt, where >10% of the Respiratory alkalosis with an increased anion gap met population has HCV. Treatment of cryoglobulinemic glomeru- abolic acidosis (Option A) is not correct because the anion lonephritis due to HCV infection is aimed at eradication of the gap is 7, and thus not exceeding the normal threshold of 8.0 virus using direct-acting antiviral drugs with or without con- to 10 mEq/L + 2.0 mEq/L (8.0-10 mmol/L + 2.0 mmol/L). comitant immunosuppression based on severity of disease. Respiratory alkalosis, normal anion gap metabolic Hepatitis A virus (Option B) infection has not been acidosis, and metabolic alkalosis (Option C) is not correct associated with specific glomerular lesions. Although hep- because the serum bicarbonate is lower, not higher, than the atitis B virus (HBV) infection and HIV infection (Options expected compensatory response. A, C) have been linked to glomerular diseases, these have Respiratory alkalosis with chronic compensation (Option classically been nephrotic syndromes, specifically membra- D) is partially correct but does not account for the serum nous nephropathy with HBV and focal segmental glomeru- bicarbonate level being lower than the expected compensatory losclerosis with HIV. This patient has a nephritic syndrome response, which indicates a concurrent metabolic acidosis. not compatible with HBV- or HIV-associated glomerular diseases. e The first step in the interpretation of acid-base disor- ders requires the identification of the likely dominant e Hepatitis C virus infection is associated with cryoglo- acid-base disorder, followed by an assessment of the bulinemic glomerulonephritis. compensatory response. e Treatment of hepatitis C-associated cryoglobulinemic e In the interpretation of acid-base disorders, when glomerulonephritis is direct-acting antiviral drugs. measured values fall outside the expected compensa- tory range, a mixed acid-base disorder is present. Bibliography Rutledge SM, Chung RT, Sise ME. Treatment of hepatitis C virus infection in Bibliography patients with mixed cryoglobulinemic syndrome and cryoglobulinemic

e The first step in the interpretation of acid-base disor- ders requires the identification of the likely dominant e Hepatitis C virus infection is associated with cryoglo- acid-base disorder, followed by an assessment of the bulinemic glomerulonephritis. compensatory response. e Treatment of hepatitis C-associated cryoglobulinemic e In the interpretation of acid-base disorders, when glomerulonephritis is direct-acting antiviral drugs. measured values fall outside the expected compensa- tory range, a mixed acid-base disorder is present. Bibliography Rutledge SM, Chung RT, Sise ME. Treatment of hepatitis C virus infection in Bibliography patients with mixed cryoglobulinemic syndrome and cryoglobulinemic Seifter JL, Chang HY. Disorders of acid-base balance: new perspectives. Kidney glomerulonephritis. Hemodial Int. 2018;22(Suppl 1):S81-S96. [PMID: Dis (Basel). 2017;2:170-186. [PMID: 28232934] doi:10.1159/000453028 29694729] doi:10.1111/hdi.12649 Item 81 Answer: D Item 82 Answer: B Educational Objective: Diagnose hepatitis C virus Educational Objective: Treat hypertension in a patient infection as the cause of cryoglobulinemic glomerulone- with chronic kidney disease and an estimated glomerular phritis. filtration rate <30 mL/min/1.73 m?.

Item 81 Answer: D Item 82 Answer: B Educational Objective: Diagnose hepatitis C virus Educational Objective: Treat hypertension in a patient infection as the cause of cryoglobulinemic glomerulone- with chronic kidney disease and an estimated glomerular phritis. filtration rate <30 mL/min/1.73 m?. The most appropriate viral study to perform is hepatitis C The most appropriate treatment for this patient is to discon- virus (HCV) antibody testing (Option D), and if positive, tinue hydrochlorothiazide and begin furosemide (Option B). 161

Answers and Critiques Because sodium retention and volume overload are major kidney disease. Assessment for urine protein is indicated contributory factors in the hypertension of chronic kidney in patients with any suspected kidney disease. Albumin is disease (CKD), dietary sodium restriction to <2000 mg/d and the predominant protein detected on urine dipstick. How- addition of a diuretic are both essential for control of blood ever, although proteinuria is most commonly comprised pressure (BP), especially in advanced CKD. Higher doses of of albumin, other proteins, including kidney-derived low- diuretics are required in patients with CKD due to decreased molecular-weight proteins, monoclonal immunoglobulins glomerular filtration rate (GFR). Hydrochlorothiazide is not and light chains, myoglobin, and hemoglobin, may be pres- an effective diuretic in this patient who has advanced CKD ent. In this case, there was a discrepancy between the semi- with an estimated GFR (eGFR) <20 to 30 mL/min/1.73 m’, quantification of urine protein by dipstick and the urine as evidenced by his elevated BP, lower extremity edema, and protein-creatinine ratio, which raises concern for the excre- hyperkalemia after 1 month of treatment. Loop diuretics, tion of protein other than albumin. In addition, the patient dosed two or three times daily, are more potent diuretics and also has a normocytic, normochromic anemia. The combi- b=] preferred in patients who have advanced CKD with an eGFR nation of these findings strongly suggests the possibility of = i) <20 to 30 mL/min/1.73 m?. multiple myeloma. A urine electrophoresis and urine exam- = Eplerenone (Option A) is not appropriate treatment for ination for light chains should be performed to help establish @o this patient because of several factors. The addition of an the diagnosis. = wn m@ aldosterone receptor blocker such as eplerenone to an ACE A repeat urinalysis (Option A) will not clarify the J fo inhibitor such as lisinopril will result in dual renin-angio- discrepancy between the urine dipstick and urine protein- (@) = tensin system inhibition and will further increase the serum creatinine ratio. The urine protein-creatinine ratio has =. potassium level. Additionally, potassium-sparing diuretics, identified significant proteinuria, which now must be 2 t= such as aldosterone receptor blockers (spironolactone or investigated. Oo nn eplerenone) or epithelial sodium channel blockers (ami- Quantification of proteinuria has traditionally been loride), are weaker diuretics. Although aldosterone receptor performed with a 24-hour urine collection (Option B), blockers are recommended for certain patients with resis- which measures all proteins present in the urine. Due to tant hypertension, they are not first-line diuretic agents challenges in feasibility, accuracy, and patient adherence, for BP management in patients with CKD and eGFR <20 to measurement of proteinuria is now typically performed by 30 mL/min /1.73 m?. determining the ratio of protein or albumin to creatinine on Increasing this patient’s dose of hydrochlorothiazide random urine samples. These ratios are easily obtained and (Option C) will not reduce this patient’s BP or edema. Thia- correlate well with timed collections. zide diuretics such as hydrochlorothiazide become increas- The sulfosalicylic acid test (Option C) can be used to ingly ineffective as GFR decreases. detect the presence of not only albumin but also other pro- According the American College of Cardiology/Amer- teins that are not detected with the urine dipstick, such as ican Heart Association, adults with hypertension and CKD urine light chains or immunoglobulins. However, this test should be treated to a BP goal of <130/80 mm Hg. Continu- will simply confirm that the urine contains nonalbumin ing the current management (Option D) is inappropriate, as proteins, which has already been determined by the urine the patient has not achieved the desired BP target, and has protein-creatinine ratio, but will not specifically identify edema and hyperkalemia. light chains or immunoglobulins. The urine albumin-creatinine ratio (Option D) mea- sures only albumin in the urine. Although this test is helpful e Sodium retention and volume overload are major con- in evaluating for diabetic kidney disease, it will not deter- tributory factors in the hypertension of chronic kidney mine the nature of the nonalbumin protein found in this disease. patient’s urine.

Because sodium retention and volume overload are major kidney disease. Assessment for urine protein is indicated contributory factors in the hypertension of chronic kidney in patients with any suspected kidney disease. Albumin is disease (CKD), dietary sodium restriction to <2000 mg/d and the predominant protein detected on urine dipstick. How- addition of a diuretic are both essential for control of blood ever, although proteinuria is most commonly comprised pressure (BP), especially in advanced CKD. Higher doses of of albumin, other proteins, including kidney-derived low- diuretics are required in patients with CKD due to decreased molecular-weight proteins, monoclonal immunoglobulins glomerular filtration rate (GFR). Hydrochlorothiazide is not and light chains, myoglobin, and hemoglobin, may be pres- an effective diuretic in this patient who has advanced CKD ent. In this case, there was a discrepancy between the semi- with an estimated GFR (eGFR) <20 to 30 mL/min/1.73 m’, quantification of urine protein by dipstick and the urine as evidenced by his elevated BP, lower extremity edema, and protein-creatinine ratio, which raises concern for the excre- hyperkalemia after 1 month of treatment. Loop diuretics, tion of protein other than albumin. In addition, the patient dosed two or three times daily, are more potent diuretics and also has a normocytic, normochromic anemia. The combi- b=] preferred in patients who have advanced CKD with an eGFR nation of these findings strongly suggests the possibility of = i) <20 to 30 mL/min/1.73 m?. multiple myeloma. A urine electrophoresis and urine exam- = Eplerenone (Option A) is not appropriate treatment for ination for light chains should be performed to help establish @o this patient because of several factors. The addition of an the diagnosis. = wn m@ aldosterone receptor blocker such as eplerenone to an ACE A repeat urinalysis (Option A) will not clarify the J fo inhibitor such as lisinopril will result in dual renin-angio- discrepancy between the urine dipstick and urine protein- (@) = tensin system inhibition and will further increase the serum creatinine ratio. The urine protein-creatinine ratio has =. potassium level. Additionally, potassium-sparing diuretics, identified significant proteinuria, which now must be 2 t= such as aldosterone receptor blockers (spironolactone or investigated. Oo nn eplerenone) or epithelial sodium channel blockers (ami- Quantification of proteinuria has traditionally been loride), are weaker diuretics. Although aldosterone receptor performed with a 24-hour urine collection (Option B), blockers are recommended for certain patients with resis- which measures all proteins present in the urine. Due to tant hypertension, they are not first-line diuretic agents challenges in feasibility, accuracy, and patient adherence, for BP management in patients with CKD and eGFR <20 to measurement of proteinuria is now typically performed by 30 mL/min /1.73 m?. determining the ratio of protein or albumin to creatinine on Increasing this patient’s dose of hydrochlorothiazide random urine samples. These ratios are easily obtained and (Option C) will not reduce this patient’s BP or edema. Thia- correlate well with timed collections. zide diuretics such as hydrochlorothiazide become increas- The sulfosalicylic acid test (Option C) can be used to ingly ineffective as GFR decreases. detect the presence of not only albumin but also other pro- According the American College of Cardiology/Amer- teins that are not detected with the urine dipstick, such as ican Heart Association, adults with hypertension and CKD urine light chains or immunoglobulins. However, this test should be treated to a BP goal of <130/80 mm Hg. Continu- will simply confirm that the urine contains nonalbumin ing the current management (Option D) is inappropriate, as proteins, which has already been determined by the urine the patient has not achieved the desired BP target, and has protein-creatinine ratio, but will not specifically identify edema and hyperkalemia. light chains or immunoglobulins. The urine albumin-creatinine ratio (Option D) mea- sures only albumin in the urine. Although this test is helpful e Sodium retention and volume overload are major con- in evaluating for diabetic kidney disease, it will not deter- tributory factors in the hypertension of chronic kidney mine the nature of the nonalbumin protein found in this disease. patient’s urine. e Loop diuretics, dosed two or three times daily, are preferred to thiazide diuretics in patients with hyper- e The presence of significant measured proteinuria via tension and an estimated glomerular filtration rate urine protein-creatinine ratio in the context of minimal <20 to 30 mL/min/1.73 m?. proteinuria on urine dipstick suggests the presence nonalbumin proteinuria. Bibliography Hamrahian SM, Falkner B. Hypertension in chronic kidney disease. Adv Exp ¢ Nonalbumin proteinuria may include kidney-derived Med Biol. 2017;956:307-325. [PMID: 27873228] doi:10.1007/5584_2016_84 low-molecular-weight proteins, monoclonal immu- noglobulins and light chains, myoglobin, and hemo- Item 83 Answer: E globin.

e Loop diuretics, dosed two or three times daily, are preferred to thiazide diuretics in patients with hyper- e The presence of significant measured proteinuria via tension and an estimated glomerular filtration rate urine protein-creatinine ratio in the context of minimal <20 to 30 mL/min/1.73 m?. proteinuria on urine dipstick suggests the presence nonalbumin proteinuria. Bibliography Hamrahian SM, Falkner B. Hypertension in chronic kidney disease. Adv Exp ¢ Nonalbumin proteinuria may include kidney-derived Med Biol. 2017;956:307-325. [PMID: 27873228] doi:10.1007/5584_2016_84 low-molecular-weight proteins, monoclonal immu- noglobulins and light chains, myoglobin, and hemo- Item 83 Answer: E globin. Educational Objective: Evaluate the cause of proteinuria. Bibliography The most appropriate test to perform next is a urine protein Echeverry G, Hortin GL, Rai AJ. Introduction to urinalysis: historical per- electrophoresis (Option E). This patient has an unexplained spectives and clinical application. Methods Mol Biol. 2010;641:1-12. elevation of serum creatinine, indicating the presence of [PMID: 20407938] doi:10.1007/978-1-60761-711-2_1 162

_Anpware ang Gritiqies Item 84 Answer: C Bibliography Leung J, Crook M. Disorders of phosphate metabolism. J Clin Pathol. 2019; Educational Objective: Diagnose rhabdomyolysis as a 72:741-747. [PMID: 31467040] doi:10.1136/jclinpath-2018-205130 cause of hyperphosphatemia.

Item 84 Answer: C Bibliography Leung J, Crook M. Disorders of phosphate metabolism. J Clin Pathol. 2019; Educational Objective: Diagnose rhabdomyolysis as a 72:741-747. [PMID: 31467040] doi:10.1136/jclinpath-2018-205130 cause of hyperphosphatemia. The most likely cause of this patient’s hyperphosphatemia Item 85 Answer: D is atorvastatin-induced rhabdomyolysis (Option C) and is evidenced by the patient’s elevated serum creatine kinase Educational Objective: Diagnose renal vein thrombosis. level. The cause of hyperphosphatemia can often be deter- The most appropriate diagnostic test to perform next is renal mined from the clinical history and is most commonly due to ultrasonography with Doppler (Option D). This patient most chronic kidney disease (CKD) or acute kidney injury. Because likely has renal vein thrombosis (RVT), a complication of phosphate is primarily an intracellular anion, widespread the hypercoagulable state of the nephrotic syndrome. Of cellular damage as occurs in rhabdomyolysis and tumor lysis the nephrotic states, RVT appears more commonly with syndrome increases serum phosphate, especially if the glo- 14] membranous nephropathy (MN) than with other patholo- o merular filtration rate (GFR) is decreased. Hyperphospha- 3 gies. Hematuria and flank pain are suggestive in this patient, a temia can also be associated with diabetic ketoacidosis and, =

The most likely cause of this patient’s hyperphosphatemia Item 85 Answer: D is atorvastatin-induced rhabdomyolysis (Option C) and is evidenced by the patient’s elevated serum creatine kinase Educational Objective: Diagnose renal vein thrombosis. level. The cause of hyperphosphatemia can often be deter- The most appropriate diagnostic test to perform next is renal mined from the clinical history and is most commonly due to ultrasonography with Doppler (Option D). This patient most chronic kidney disease (CKD) or acute kidney injury. Because likely has renal vein thrombosis (RVT), a complication of phosphate is primarily an intracellular anion, widespread the hypercoagulable state of the nephrotic syndrome. Of cellular damage as occurs in rhabdomyolysis and tumor lysis the nephrotic states, RVT appears more commonly with syndrome increases serum phosphate, especially if the glo- 14] membranous nephropathy (MN) than with other patholo- o merular filtration rate (GFR) is decreased. Hyperphospha- 3 gies. Hematuria and flank pain are suggestive in this patient, a temia can also be associated with diabetic ketoacidosis and, = although RVT can be asymptomatic. The gold standard diag- less commonly, lactic acidosis. Excessive phosphate intake = nostic test for RVT is selective renal venography. However, less i rarely causes hyperphosphatemia because the kidney rapidly <c invasive procedures are more typically used. In this patient i excretes phosphate. However, phosphate-containing cathar- with acute kidney injury (AKI) (or an estimated glomerular 6 tics can cause acute elevations in serum phosphate, especially ne filtration rate of <30 mL/min/1.73 m2), itis preferable to avoid ® in patients with reduced GFR. The risk for statin-induced contrast exposure. The imaging study of first choice is ultra- = serious muscle injury, including rhabdomyolysis, is <0.1%. wv sonography with Doppler. If the test is negative and a high c Discontinuation of the statin in a patient with statin-induced <= index of suspicion persists, then renal venography could be myopathy is typically followed by a decreasing creatine kinase considered. and resolution of symptoms, but recovery can be prolonged in Anti-phospholipase receptor A2 antibodies (Option A) patients with more severe muscle injury. are present in approximately 70% of patients with MN and Although hyperphosphatemia is common in stage G4 are emerging as a diagnostic and prognostic tool to identify or G5 CKD (Option A), it is unusual with the mild degree and monitor disease. However, this test has no role in defin- of kidney dysfunction seen in this patient. With decreasing ing the etiology of AKI when underlying MN is known or in GFR, there is an increase in fibroblast growth factor 23, advancing the diagnosis of RVT. which not only decreases the reabsorption of phosphorus in In patients with oliguria, the fractional excretion of the renal proximal tubule but also inhibits 1-hydroxylation sodium (FEy,) (Option B) can help distinguish between of vitamin D. This results in increased renal phosphorus prerenal AKI and acute tubular necrosis. In prerenal AKI excretion and decreased absorption of phosphorus from the the FEy, is <1%. However, FEy, <1% can occur in other gastrointestinal tract, thus maintaining serum phosphorus conditions, including contrast nephropathy, pigment until late-stage CKD, at which time these homeostatic mech- nephropathy, glomerulonephritis, and early obstruction. anisms are no longer able to counter the decrease in renal FEy, >2% is consistent with acute tubular necrosis. How- phosphorus excretion. ever, FEx, may be >2% in patients with prerenal AKI who Because insulin stimulates the sodium-dependent have urinary sodium loss due to diuretics, have adrenal phosphorus transporter, hyperphosphatemia may occur in insufficiency, or from bicarbonaturia in severe metabolic patients with insulin deficiency (Option B) due to decreased alkalosis. This patient is not oliguric and the presence cellular uptake of phosphate. However, these patients of AKI in a patient with MN, hematuria, and flank pain develop hyperphosphaturia and subsequent hypophospha- strongly suggests RVT. temia due to the effect of hyperglycosuric osmotic diuresis. Although radionuclide imaging (Option C) may help Vitamin D toxicity (Option D) can cause hyperphospha- assess if there is arterial flow to the kidney as well as esti- temia but typically in cases of ingestion of large quantities. In mate the glomerular filtration rate, it will not identify RVT addition, vitamin D-induced hyperphosphatemia is associ- with specificity. ated with elevated serum calcium levels, which are not seen in this patient.

although RVT can be asymptomatic. The gold standard diag- less commonly, lactic acidosis. Excessive phosphate intake = nostic test for RVT is selective renal venography. However, less i rarely causes hyperphosphatemia because the kidney rapidly <c invasive procedures are more typically used. In this patient i excretes phosphate. However, phosphate-containing cathar- with acute kidney injury (AKI) (or an estimated glomerular 6 tics can cause acute elevations in serum phosphate, especially ne filtration rate of <30 mL/min/1.73 m2), itis preferable to avoid ® in patients with reduced GFR. The risk for statin-induced contrast exposure. The imaging study of first choice is ultra- = serious muscle injury, including rhabdomyolysis, is <0.1%. wv sonography with Doppler. If the test is negative and a high c Discontinuation of the statin in a patient with statin-induced <= index of suspicion persists, then renal venography could be myopathy is typically followed by a decreasing creatine kinase considered. and resolution of symptoms, but recovery can be prolonged in Anti-phospholipase receptor A2 antibodies (Option A) patients with more severe muscle injury. are present in approximately 70% of patients with MN and Although hyperphosphatemia is common in stage G4 are emerging as a diagnostic and prognostic tool to identify or G5 CKD (Option A), it is unusual with the mild degree and monitor disease. However, this test has no role in defin- of kidney dysfunction seen in this patient. With decreasing ing the etiology of AKI when underlying MN is known or in GFR, there is an increase in fibroblast growth factor 23, advancing the diagnosis of RVT. which not only decreases the reabsorption of phosphorus in In patients with oliguria, the fractional excretion of the renal proximal tubule but also inhibits 1-hydroxylation sodium (FEy,) (Option B) can help distinguish between of vitamin D. This results in increased renal phosphorus prerenal AKI and acute tubular necrosis. In prerenal AKI excretion and decreased absorption of phosphorus from the the FEy, is <1%. However, FEy, <1% can occur in other gastrointestinal tract, thus maintaining serum phosphorus conditions, including contrast nephropathy, pigment until late-stage CKD, at which time these homeostatic mech- nephropathy, glomerulonephritis, and early obstruction. anisms are no longer able to counter the decrease in renal FEy, >2% is consistent with acute tubular necrosis. How- phosphorus excretion. ever, FEx, may be >2% in patients with prerenal AKI who Because insulin stimulates the sodium-dependent have urinary sodium loss due to diuretics, have adrenal phosphorus transporter, hyperphosphatemia may occur in insufficiency, or from bicarbonaturia in severe metabolic patients with insulin deficiency (Option B) due to decreased alkalosis. This patient is not oliguric and the presence cellular uptake of phosphate. However, these patients of AKI in a patient with MN, hematuria, and flank pain develop hyperphosphaturia and subsequent hypophospha- strongly suggests RVT. temia due to the effect of hyperglycosuric osmotic diuresis. Although radionuclide imaging (Option C) may help Vitamin D toxicity (Option D) can cause hyperphospha- assess if there is arterial flow to the kidney as well as esti- temia but typically in cases of ingestion of large quantities. In mate the glomerular filtration rate, it will not identify RVT addition, vitamin D-induced hyperphosphatemia is associ- with specificity. ated with elevated serum calcium levels, which are not seen in this patient. e Renal vein thrombosis is a complication of the nephrotic syndrome and is most commonly associated e The cause of hyperphosphatemia can often be deter- with membranous nephropathy. mined from the clinical history and is most commonly e Preferred imaging studies for suspected renal vein throm- due to chronic kidney disease or acute kidney injury. bosis in patients with acute kidney injury or an estimated e Rhabdomyolysis and tumor lysis syndrome increase glomerular filtration rate of <30 mL/min/1.73 m? include serum phosphate levels acutely due to widespread renal ultrasonography with Doppler and renal veno- cellular damage. graphy.

e Renal vein thrombosis is a complication of the nephrotic syndrome and is most commonly associated e The cause of hyperphosphatemia can often be deter- with membranous nephropathy. mined from the clinical history and is most commonly e Preferred imaging studies for suspected renal vein throm- due to chronic kidney disease or acute kidney injury. bosis in patients with acute kidney injury or an estimated e Rhabdomyolysis and tumor lysis syndrome increase glomerular filtration rate of <30 mL/min/1.73 m? include serum phosphate levels acutely due to widespread renal ultrasonography with Doppler and renal veno- cellular damage. graphy. 163

Answers and Critiques Bibliography ltem 87 Answer: A Barbour SJ, Greenwald A, Djurdjev O, et al. Disease-specific risk of venous Educational Objective: Diagnose Gitelman syndrome. thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012;81:190-195. [PMID: 21918501] doi:10.1038/ki.2011.312 The most likely diagnosis is Gitelman syndrome (Option A), an autosomal recessive disorder that causes decreased activ- ity in the sodium chloride transporter in the distal tubule. Item 86 Answer: D This patient has a hypokalemic metabolic alkalosis with a Educational Objective: Manage hemodialysis line- low-normal blood pressure. The differential of this presenta- related sepsis. tion includes surreptitious vomiting, diuretic abuse, Bartter The most appropriate additional management is to remove syndrome, and Gitelman syndrome. These patients have find- the tunneled hemodialysis catheter (Option D). Infection is ings similar to those in patients being treated with thiazide the second leading cause of death in patients with end-stage diuretics. Patients with Gitelman syndrome typically present

Bibliography ltem 87 Answer: A Barbour SJ, Greenwald A, Djurdjev O, et al. Disease-specific risk of venous Educational Objective: Diagnose Gitelman syndrome. thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012;81:190-195. [PMID: 21918501] doi:10.1038/ki.2011.312 The most likely diagnosis is Gitelman syndrome (Option A), an autosomal recessive disorder that causes decreased activ- ity in the sodium chloride transporter in the distal tubule. Item 86 Answer: D This patient has a hypokalemic metabolic alkalosis with a Educational Objective: Manage hemodialysis line- low-normal blood pressure. The differential of this presenta- related sepsis. tion includes surreptitious vomiting, diuretic abuse, Bartter The most appropriate additional management is to remove syndrome, and Gitelman syndrome. These patients have find- the tunneled hemodialysis catheter (Option D). Infection is ings similar to those in patients being treated with thiazide the second leading cause of death in patients with end-stage diuretics. Patients with Gitelman syndrome typically present > kidney disease (ESKD). Patients are at increased risk due to a in late adolescence or early adulthood with low-normal blood = pressure and hypokalemic metabolic alkalosis. Frequently, wn relatively immunosuppressed state from chronic inflamma- = tion and frequent exposure to the health care environment. they will have hypomagnesemia and a high-normal serum @ =~ Ww Tunneled dialysis catheters increase the risk for bacteremia, calcium level. They will have low urine calcium excretion, as os and empiric antibiotics should be administered while await- seen in this patient, and their urine diuretic screen will be neg- = a. ing blood culture results in patients with suspected bactere- ative. Bartter syndrome, which affects transport in the loop of 2) =f mia. Tunneled catheters should be removed immediately for Henle, has a similar presentation to Gitelman syndrome. How- =. severe sepsis, evidence of metastatic infection, evidence of an ever, Bartter syndrome typically presents in early childhood 2 i exit-site or tunnel infection, persistent fever, or bacteremia and is far less common than Gitelman syndrome. Because of oO wr despite administration of antibiotics. significant sodium wasting, these patients will often have epi- Antibiotic lock therapy (Option A) consists of the instil- sodes of kidney injury due to hypotension. If measured, they lation of a highly concentrated antibiotic solution into an typically have a normal-to-increased urine calcium. intravascular catheter lumen to treat catheter-related blood- Patients who abuse laxatives (Option B) typically have a stream infections. Antibiotic lock therapy with vancomycin low urine chloride and proportionally low sodium and potas- and/or ceftazidime is an alternative option for stable patients sium excretion and frequently have a normal anion gap met- with less virulent organisms such as Staphylococcus epi- abolic acidosis. In this case, the urine anion gap will be pos- dermitis, but catheter salvage should not be attempted for itive, reflecting increase urinary excretion of hydrogen ions. patients with severe sepsis, Staphylococcus aureus infec- Urine Anion Gap = (Urine Sodium + Urine Potassium) tions, and some gram-negative organisms. ~ Urine Chloride Arteriovenous fistula (AVF) excision (Option B) is not indicated. Hemodialysis arm-access sites have a lower risk The presence of metabolic alkalosis excludes laxative

> kidney disease (ESKD). Patients are at increased risk due to a in late adolescence or early adulthood with low-normal blood = pressure and hypokalemic metabolic alkalosis. Frequently, wn relatively immunosuppressed state from chronic inflamma- = tion and frequent exposure to the health care environment. they will have hypomagnesemia and a high-normal serum @ =~ Ww Tunneled dialysis catheters increase the risk for bacteremia, calcium level. They will have low urine calcium excretion, as os and empiric antibiotics should be administered while await- seen in this patient, and their urine diuretic screen will be neg- = a. ing blood culture results in patients with suspected bactere- ative. Bartter syndrome, which affects transport in the loop of 2) =f mia. Tunneled catheters should be removed immediately for Henle, has a similar presentation to Gitelman syndrome. How- =. severe sepsis, evidence of metastatic infection, evidence of an ever, Bartter syndrome typically presents in early childhood 2 i exit-site or tunnel infection, persistent fever, or bacteremia and is far less common than Gitelman syndrome. Because of oO wr despite administration of antibiotics. significant sodium wasting, these patients will often have epi- Antibiotic lock therapy (Option A) consists of the instil- sodes of kidney injury due to hypotension. If measured, they lation of a highly concentrated antibiotic solution into an typically have a normal-to-increased urine calcium. intravascular catheter lumen to treat catheter-related blood- Patients who abuse laxatives (Option B) typically have a stream infections. Antibiotic lock therapy with vancomycin low urine chloride and proportionally low sodium and potas- and/or ceftazidime is an alternative option for stable patients sium excretion and frequently have a normal anion gap met- with less virulent organisms such as Staphylococcus epi- abolic acidosis. In this case, the urine anion gap will be pos- dermitis, but catheter salvage should not be attempted for itive, reflecting increase urinary excretion of hydrogen ions. patients with severe sepsis, Staphylococcus aureus infec- Urine Anion Gap = (Urine Sodium + Urine Potassium) tions, and some gram-negative organisms. ~ Urine Chloride Arteriovenous fistula (AVF) excision (Option B) is not indicated. Hemodialysis arm-access sites have a lower risk The presence of metabolic alkalosis excludes laxative for infection than do catheters; AVFs have the lowest risk abuse as the cause of hypokalemia in this patient.

> kidney disease (ESKD). Patients are at increased risk due to a in late adolescence or early adulthood with low-normal blood = pressure and hypokalemic metabolic alkalosis. Frequently, wn relatively immunosuppressed state from chronic inflamma- = tion and frequent exposure to the health care environment. they will have hypomagnesemia and a high-normal serum @ =~ Ww Tunneled dialysis catheters increase the risk for bacteremia, calcium level. They will have low urine calcium excretion, as os and empiric antibiotics should be administered while await- seen in this patient, and their urine diuretic screen will be neg- = a. ing blood culture results in patients with suspected bactere- ative. Bartter syndrome, which affects transport in the loop of 2) =f mia. Tunneled catheters should be removed immediately for Henle, has a similar presentation to Gitelman syndrome. How- =. severe sepsis, evidence of metastatic infection, evidence of an ever, Bartter syndrome typically presents in early childhood 2 i exit-site or tunnel infection, persistent fever, or bacteremia and is far less common than Gitelman syndrome. Because of oO wr despite administration of antibiotics. significant sodium wasting, these patients will often have epi- Antibiotic lock therapy (Option A) consists of the instil- sodes of kidney injury due to hypotension. If measured, they lation of a highly concentrated antibiotic solution into an typically have a normal-to-increased urine calcium. intravascular catheter lumen to treat catheter-related blood- Patients who abuse laxatives (Option B) typically have a stream infections. Antibiotic lock therapy with vancomycin low urine chloride and proportionally low sodium and potas- and/or ceftazidime is an alternative option for stable patients sium excretion and frequently have a normal anion gap met- with less virulent organisms such as Staphylococcus epi- abolic acidosis. In this case, the urine anion gap will be pos- dermitis, but catheter salvage should not be attempted for itive, reflecting increase urinary excretion of hydrogen ions. patients with severe sepsis, Staphylococcus aureus infec- Urine Anion Gap = (Urine Sodium + Urine Potassium) tions, and some gram-negative organisms. ~ Urine Chloride Arteriovenous fistula (AVF) excision (Option B) is not indicated. Hemodialysis arm-access sites have a lower risk The presence of metabolic alkalosis excludes laxative for infection than do catheters; AVFs have the lowest risk abuse as the cause of hypokalemia in this patient. compared with arteriovenous grafts. This patient has no evi- Primary hyperaldosteronism (Option C) results from the dence of an AVF-related infection, nor is it expected, as his autonomous secretion of excessive aldosterone. It is relatively

for infection than do catheters; AVFs have the lowest risk abuse as the cause of hypokalemia in this patient. compared with arteriovenous grafts. This patient has no evi- Primary hyperaldosteronism (Option C) results from the dence of an AVF-related infection, nor is it expected, as his autonomous secretion of excessive aldosterone. It is relatively AVF has not yet been used for dialysis. common, occurring in approximately 10% of patients with Exchange of the catheter over a guidewire (Option C) hypertension. Additional signs of primary hyperaldosteronism may be an option for clinically stable patients without a tun- include hypokalemia and metabolic alkalosis. The patient’s nel infection or for patients who clear the bacteremia within low blood pressure excludes primary hyperaldosteronism as 48 hours of antibiotic administration. This patient meets the cause of her hypokalemia and metabolic alkalosis.

may be an option for clinically stable patients without a tun- include hypokalemia and metabolic alkalosis. The patient’s nel infection or for patients who clear the bacteremia within low blood pressure excludes primary hyperaldosteronism as 48 hours of antibiotic administration. This patient meets the cause of her hypokalemia and metabolic alkalosis. none of these indications for catheter exchange. Patients with surreptitious vomiting (Option D) will have a hypokalemic metabolic alkalosis and low-normal blood pressure similar to that seen in patients with Gitelman ¢ Tunneled catheters should be removed immediately for syndrome; however, urine chloride will be low and urine severe sepsis, evidence of metastatic infection, evidence calcium excretion should not be low. of an exit-site or tunnel infection, persistent fever, or bacteremia despite administration of antibiotics. e Patients with Gitelman syndrome typically present in e Antibiotic lock therapy with vancomycin and/or cef- late adolescence or early adulthood with low-normal tazidime is an alternative option to treat catheter-related blood pressure, hypokalemic metabolic alkalosis, and, bloodstream infections in stable patients with less viru- frequently, hypomagnesemia and high-normal serum lent organisms such as Staphylococcus epidermitis. calcium levels.

none of these indications for catheter exchange. Patients with surreptitious vomiting (Option D) will have a hypokalemic metabolic alkalosis and low-normal blood pressure similar to that seen in patients with Gitelman ¢ Tunneled catheters should be removed immediately for syndrome; however, urine chloride will be low and urine severe sepsis, evidence of metastatic infection, evidence calcium excretion should not be low. of an exit-site or tunnel infection, persistent fever, or bacteremia despite administration of antibiotics. e Patients with Gitelman syndrome typically present in e Antibiotic lock therapy with vancomycin and/or cef- late adolescence or early adulthood with low-normal tazidime is an alternative option to treat catheter-related blood pressure, hypokalemic metabolic alkalosis, and, bloodstream infections in stable patients with less viru- frequently, hypomagnesemia and high-normal serum lent organisms such as Staphylococcus epidermitis. calcium levels. Bibliography Bibliography Johns TS, Mokrzycki MH. Optimal approach for the diagnosis of hemodialy- Fulchiero R, Seo-Mayer P. Bartter syndrome and Gitelman syndrome. sis catheter-related bacteremia [Editorial]. Clin J Am Soc Nephrol. Pediatr Clin North Am. 2019;66:121-134. [PMID: 30454738] doi:10.1016/j. 2016;11:756-758. [PMID: 27037273] doi:10.2215/CJN.02910316 pel.2018.08.010 164

_ Answers and Critiques of blood cholesterol: executive summary: a report of the American Item 88 Answer: D College of Cardiology/American Heart Association Task Force on Clinical Educational Objective: Prevent cardiovascular events in Practice Guidelines. Circulation. 2019;139:e1046-e1081. [PMID: 30565953] doi:10.1161/CIR.0000000000000624 a patient with chronic kidney disease. The most appropriate treatment to reduce this patient’s risk of atherosclerotic cardiovascular disease (ASCVD) is Item 89 Answer: C moderate-intensity atorvastatin (Option D). The American Educational Objective: Diagnose hepatitis C virus College of Cardiology/American Heart Association Guide- infection as the cause of membranoproliferative line on the Management of Blood Cholesterol recommends glomerulonephritis. moderate-intensity statin therapy for any patient aged 40 to 75 years with diabetes mellitus. In addition, this guideline The most likely cause of this patient’s glomerulonephritis is recognizes chronic kidney disease (CKD) as a risk enhancer hepatitis C virus (HCV) infection (Option C). This patient has for ASCVD and recommends a moderate-intensity statin for membranoproliferative glomerulonephritis (MPGN). Based wn o adults aged 40 to 75 years with an LDL cholesterol of 70 to on her history of transactional sex, she is at increased risk as

recognizes chronic kidney disease (CKD) as a risk enhancer hepatitis C virus (HCV) infection (Option C). This patient has for ASCVD and recommends a moderate-intensity statin for membranoproliferative glomerulonephritis (MPGN). Based wn o adults aged 40 to 75 years with an LDL cholesterol of 70 to on her history of transactional sex, she is at increased risk as 189 mg/dL (1.81-4.89 mmol/L) who have a 10-year ASCVD for HCV infection, which is a secondary cause of immune = risk >7.5% (excluding patients treated with dialysis or kidney complex-mediated MPGN. If the patient tests positive for = cs) transplantation). The Kidney Disease: Improving Global Out- HCV, treatment of the lesion would involve anti-HCV antiviral | comes guidelines recommend treatment with a statin in all therapy and consideration of immunosuppression (glucocor- S ro] patients aged >50 years with non-dialysis-dependent CKD ticoids plus rituximab). The approach to evaluating MPGN wn ed and in adults aged 18 to 49 years with non-dialysis-dependent lesions on kidney biopsy is based on the pattern of staining on o

189 mg/dL (1.81-4.89 mmol/L) who have a 10-year ASCVD for HCV infection, which is a secondary cause of immune = risk >7.5% (excluding patients treated with dialysis or kidney complex-mediated MPGN. If the patient tests positive for = cs) transplantation). The Kidney Disease: Improving Global Out- HCV, treatment of the lesion would involve anti-HCV antiviral | comes guidelines recommend treatment with a statin in all therapy and consideration of immunosuppression (glucocor- S ro] patients aged >50 years with non-dialysis-dependent CKD ticoids plus rituximab). The approach to evaluating MPGN wn ed and in adults aged 18 to 49 years with non-dialysis-dependent lesions on kidney biopsy is based on the pattern of staining on o immunofluorescence microscopy. The more common pattern = CKD and any one of the following: coronary disease, diabetes, wn = prior ischemic stroke, or a >10% estimated risk for coronary is immune complex deposition with both immunoglobu- =z death or nonfatal myocardial infarction. The use of statins to lin (IgG, IgM, and/or IgA) and complement (Clq and/or C3) treat dyslipidemia in patients with CKD has been shown to on immunofluorescence, which infers an inciting cause or

immunofluorescence microscopy. The more common pattern = CKD and any one of the following: coronary disease, diabetes, wn = prior ischemic stroke, or a >10% estimated risk for coronary is immune complex deposition with both immunoglobu- =z death or nonfatal myocardial infarction. The use of statins to lin (IgG, IgM, and/or IgA) and complement (Clq and/or C3) treat dyslipidemia in patients with CKD has been shown to on immunofluorescence, which infers an inciting cause or reduce cardiovascular events. However, statins do not slow event that generally falls into one of three major categories: progression of CKD. When patients reach end-stage kidney infectious, autoimmune, or malignancy associated. The most disease, statins do not reduce cardiovascular events. Atorva- common of these etiologies is infectious, specifically infection statin is frequently chosen for patients with CKD because it with HCV. undergoes hepatic clearance and does not require renal dose A test for genetic mutations of alternative complement adjustments. In addition, atorvastatin may have beneficial pathway proteins (Option A) is not indicated. This extremely effects on proteinuria. rare finding manifests as a MPGN lesion showing only C3 There is no indication for either evolocumab or ezeti- (without immunoglobulin or Clq staining) on immunofluo- mibe (Options A, B). The proprotein convertase subtilisin/ rescence staining. This suggests an antibody-independent kexin type 9 (PCSK9) inhibitors, such as evolocumab, are means of complement activation and points to hyperactivity monoclonal antibodies that bind to serine protease PCSK9, of the alternative complement pathway. These C3 glomeru- a liver enzyme that degrades hepatocyte LDL receptors. lopathies, named for the isolated C3 staining pattern seen on

kexin type 9 (PCSK9) inhibitors, such as evolocumab, are means of complement activation and points to hyperactivity monoclonal antibodies that bind to serine protease PCSK9, of the alternative complement pathway. These C3 glomeru- a liver enzyme that degrades hepatocyte LDL receptors. lopathies, named for the isolated C3 staining pattern seen on Adding a PCSK9 inhibitor can be considered for secondary immunofluorescence, should prompt screening for genetic prevention in very high-risk patients if the LDL cholesterol abnormalities in alternative complement pathway proteins. level remains >70 mg/dL (1.81 mmol/L) or the non-HDL cho- This patient has immune complex deposition with the pres- lesterol level is >100 mg/dL (2.59 mmol/L) despite maximally ence of both immunoglobulin and complement; therefore, tolerated lipid-lowering therapy. Ezetimibe can be added to testing for alternate pathway mutations is not indicated. maximally tolerated statin therapy in very high-risk patients Hepatitis B virus infection and syphilis (Options B, D) with clinically evident ASCVD when the LDL cholesterol have been linked to glomerular diseases, but these classically level remains >70 mg/dL (1.81 mmol/L). present with the nephrotic syndrome associated with mem- High-intensity statin therapy is not indicated in this branous nephropathy. patient, and atorvastatin is usually preferred to rosuvastatin (Option C), a renally excreted statin, in patients with CKD. e The immune complex form of membranoproliferative glomerulonephritis is associated with infectious, e The use of statins to treat dyslipidemia in patients autoimmune, or malignancy-associated etiologies. with chronic kidney disease has been shown to ¢ The most common etiology of immune complex reduce cardiovascular events. membranoproliferative glomerulonephritis is infec- e Statins do not slow progression of chronic kidney disease. tious, specifically hepatitis C virus infection.

with chronic kidney disease has been shown to ¢ The most common etiology of immune complex reduce cardiovascular events. membranoproliferative glomerulonephritis is infec- e Statins do not slow progression of chronic kidney disease. tious, specifically hepatitis C virus infection. Bibliography Bibliography Gupta A, Quigg RJ. Glomerular diseases associated with hepatitis B and C. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ Adv Chronic Kidney Dis. 2015;22:343-351. [PMID: 26311595] doi:10.1053/j. ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management ackd.2015.06.003 165

Answers and Critiques Item 90 Answer: C Bibliography Sterns RH. Treatment of severe hyponatremia. Clin J Am Soc Nephrol. Educational Objective: Treat hyponatremia in a symp- 2018;13:641-649. [PMID: 29295830] doi:10.2215/CJN.10440917 tomatic patient.

Item 90 Answer: C Bibliography Sterns RH. Treatment of severe hyponatremia. Clin J Am Soc Nephrol. Educational Objective: Treat hyponatremia in a symp- 2018;13:641-649. [PMID: 29295830] doi:10.2215/CJN.10440917 tomatic patient. The most appropriate treatment is 3% saline plus desmo- pressin (Option C). The first step when treating symptomatic Item 91 Answer: D hyponatremia is determining whether it is an acute (<48 Educational Objective: Screen for albuminuria to hours) or a chronic (>48 hours) presentation. For this patient determine optimal treatment of hypertension. with confusion, it cannot be determined how long the serum sodium level has been low; in these cases, the hyponatre- The most appropriate additional management is to obtain a mia should always be treated as chronic. It is important to urine albumin-creatinine ratio (Option D). Dipstick mea- prevent overly rapid correction of the serum sodium. To pre- surements of protein are dependent on urine concentration; = vent swelling, the brain cell response to hyponatremia is to false-negative results may be caused by dilute urine, and = wn extrude osmotically active solutes. This volume regulatory false-positive results may be caused by highly concentrated = response occurs over 48 hours. After 48 hours, rapid increase urine. Because moderately increased albuminuria may go © = wn in the serum sodium concentration will cause brain cells undetected by dipstick urinalysis, direct quantification is rs) to acutely shrink, which can lead to osmotic demyelination required in high-risk patients. The American College of = Qa. syndrome (ODS). In symptomatic individuals with hypona- Cardiology/American Heart Association (ACC/AHA) blood Oo tremia, acutely increasing the serum sodium by 3 to 4 mEq/L pressure (BP) guideline recommendsa BP goal of <130/80 mm = =. (3-4 mmol/L) will usually improve symptoms; if the increase Hg for patients with diabetes mellitus. The American Diabetes <4 c in serum sodium is <8 mEq/L (8 mmol/L) in 24 hours, the inci- Association (ADA) recommends a BP target of <130/80 mm © n dence of ODS can be markedly decreased and often avoided. Hg for patients with diabetes and hypertension at higher Because of her symptoms, it is essential to increase the serum cardiovascular risk (existing atherosclerotic cardiovascular sodium 3 to 4 mEq/L (3-4 mmol/L) quickly by administering disease [ASCVD] or 10-year ASCVD event risk 215%), if it can either a 100-mL bolus or 30 mL/h of hypertonic 3% saline be safely attained. For patients who have diabetes and hyper- and measuring the serum sodium every 2 hours. However, tension with a 10-year ASCVD <15%, the ADA recommends if the hyponatremia is due to volume depletion or excessive a target of 140/90 mm Hg. First-line therapy in non-Black water intake, the serum sodium can rise rapidly as the kid- patients with diabetes includes a thiazide diuretic, calcium ney excretes the excess water. Simultaneous administration channel blocker (CCB), ACE inhibitor, or angiotensin recep- of desmopressin makes the rate of correction resulting from tor inhibitor (ARB). First-line therapy for Black patients is 3% saline infusion more predictable and safer for the patient a thiazide diuretic or CCB. According to the ACC/AHA, ACE because it prevents an unexpected water diuresis and rapid inhibitors or ARBs may be considered in the presence of increases in the serum sodium. albuminuria. For patients with hypertension, diabetes, and In symptomatic hyponatremic patients, fluid restriction urine albumin-creatinine ratio >300 mg/g, the ADA recom- (Option A) alone is not an appropriate treatment. The goal is mends an ACE inhibitor or ARB at the maximum tolerated to improve symptoms and prevent further neurologic com- dose as first-line treatment regardless of race or ethnicity; plication by rapidly increasing the serum sodium level by 3 such treatment should also be considered if urine albumin- to 4 mEq/L (3-4 mmol/L) with 3% saline and desmopressin creatinine ratio 230 mg/g to 300 mg/g. Consequently, the administration. next step in management of this patient is to measure her Administration of 0.9% saline (Option B) may lower the urine albumin-creatinine ratio to determine if an ACE inhib- serum sodium in patients with the syndrome of inappropri- itor or ARB is indicated. ate antidiuretic hormone secretion, because the amount of Selecting a specific antihypertensive drug, such as a sodium infused can be excreted in a smaller volume of urine CCB (amlodipine) (Option A), a thiazide diuretic (hydro- leaving behind water. chlorothiazide) (Option B), an ACE inhibitor, or an ARB is Tolvaptan (Option D), an antidiuretic hormone antag- not indicated until quantification of albuminuria is per- onist, should not be used in patients with symptomatic formed. hyponatremia, as the response is unpredictable. Patients with stage 2 hypertension should be managed with both pharmacologic and nonpharmacologic therapy. Therefore, continuing nonpharmacologic therapy only is not e The initial treatment of symptomatic hyponatremia is sufficient (Option C). After initiation of therapy, the patient’s acutely increasing the serum sodium by 3 to 4 mEq/L BP should be remeasured in 1 month, not 3 months.

The most appropriate treatment is 3% saline plus desmo- pressin (Option C). The first step when treating symptomatic Item 91 Answer: D hyponatremia is determining whether it is an acute (<48 Educational Objective: Screen for albuminuria to hours) or a chronic (>48 hours) presentation. For this patient determine optimal treatment of hypertension. with confusion, it cannot be determined how long the serum sodium level has been low; in these cases, the hyponatre- The most appropriate additional management is to obtain a mia should always be treated as chronic. It is important to urine albumin-creatinine ratio (Option D). Dipstick mea- prevent overly rapid correction of the serum sodium. To pre- surements of protein are dependent on urine concentration; = vent swelling, the brain cell response to hyponatremia is to false-negative results may be caused by dilute urine, and = wn extrude osmotically active solutes. This volume regulatory false-positive results may be caused by highly concentrated = response occurs over 48 hours. After 48 hours, rapid increase urine. Because moderately increased albuminuria may go © = wn in the serum sodium concentration will cause brain cells undetected by dipstick urinalysis, direct quantification is rs) to acutely shrink, which can lead to osmotic demyelination required in high-risk patients. The American College of = Qa. syndrome (ODS). In symptomatic individuals with hypona- Cardiology/American Heart Association (ACC/AHA) blood Oo tremia, acutely increasing the serum sodium by 3 to 4 mEq/L pressure (BP) guideline recommendsa BP goal of <130/80 mm = =. (3-4 mmol/L) will usually improve symptoms; if the increase Hg for patients with diabetes mellitus. The American Diabetes <4 c in serum sodium is <8 mEq/L (8 mmol/L) in 24 hours, the inci- Association (ADA) recommends a BP target of <130/80 mm © n dence of ODS can be markedly decreased and often avoided. Hg for patients with diabetes and hypertension at higher Because of her symptoms, it is essential to increase the serum cardiovascular risk (existing atherosclerotic cardiovascular sodium 3 to 4 mEq/L (3-4 mmol/L) quickly by administering disease [ASCVD] or 10-year ASCVD event risk 215%), if it can either a 100-mL bolus or 30 mL/h of hypertonic 3% saline be safely attained. For patients who have diabetes and hyper- and measuring the serum sodium every 2 hours. However, tension with a 10-year ASCVD <15%, the ADA recommends if the hyponatremia is due to volume depletion or excessive a target of 140/90 mm Hg. First-line therapy in non-Black water intake, the serum sodium can rise rapidly as the kid- patients with diabetes includes a thiazide diuretic, calcium ney excretes the excess water. Simultaneous administration channel blocker (CCB), ACE inhibitor, or angiotensin recep- of desmopressin makes the rate of correction resulting from tor inhibitor (ARB). First-line therapy for Black patients is 3% saline infusion more predictable and safer for the patient a thiazide diuretic or CCB. According to the ACC/AHA, ACE because it prevents an unexpected water diuresis and rapid inhibitors or ARBs may be considered in the presence of increases in the serum sodium. albuminuria. For patients with hypertension, diabetes, and In symptomatic hyponatremic patients, fluid restriction urine albumin-creatinine ratio >300 mg/g, the ADA recom- (Option A) alone is not an appropriate treatment. The goal is mends an ACE inhibitor or ARB at the maximum tolerated to improve symptoms and prevent further neurologic com- dose as first-line treatment regardless of race or ethnicity; plication by rapidly increasing the serum sodium level by 3 such treatment should also be considered if urine albumin- to 4 mEq/L (3-4 mmol/L) with 3% saline and desmopressin creatinine ratio 230 mg/g to 300 mg/g. Consequently, the administration. next step in management of this patient is to measure her Administration of 0.9% saline (Option B) may lower the urine albumin-creatinine ratio to determine if an ACE inhib- serum sodium in patients with the syndrome of inappropri- itor or ARB is indicated. ate antidiuretic hormone secretion, because the amount of Selecting a specific antihypertensive drug, such as a sodium infused can be excreted in a smaller volume of urine CCB (amlodipine) (Option A), a thiazide diuretic (hydro- leaving behind water. chlorothiazide) (Option B), an ACE inhibitor, or an ARB is Tolvaptan (Option D), an antidiuretic hormone antag- not indicated until quantification of albuminuria is per- onist, should not be used in patients with symptomatic formed. hyponatremia, as the response is unpredictable. Patients with stage 2 hypertension should be managed with both pharmacologic and nonpharmacologic therapy. Therefore, continuing nonpharmacologic therapy only is not e The initial treatment of symptomatic hyponatremia is sufficient (Option C). After initiation of therapy, the patient’s acutely increasing the serum sodium by 3 to 4 mEq/L BP should be remeasured in 1 month, not 3 months. (3-4 mmol/L) with 3% saline infusion. e In the treatment of symptomatic hyponatremia, e Because moderately increased albuminuria may go simultaneous administration of desmopressin with undetected by dipstick urinalysis, direct quantifica- 3% saline infusion results in a more predictable and tion is required in high-risk patients. safer increase in serum sodium. (Continued)

(3-4 mmol/L) with 3% saline infusion. e In the treatment of symptomatic hyponatremia, e Because moderately increased albuminuria may go simultaneous administration of desmopressin with undetected by dipstick urinalysis, direct quantifica- 3% saline infusion results in a more predictable and tion is required in high-risk patients. safer increase in serum sodium. (Continued) 166

Answers and Critiques e The American Diabetes Association recommends an e Alcoholic ketoacidosis results in an increased anion ACE inhibitor or angiotensin receptor blocker at the gap metabolic acidosis and minimal ketones on urine maximum tolerated dose as first-line treatment for dipstick analysis. hypertension in patients with diabetes mellitus and e Ethylene glycol, methanol, and isopropyl alcohol tox- urine albumin-creatinine ratio >300 mg/g. icities are associated with an increased osmolal gap. Bibliography Bibliography American Diabetes Association. 10. Cardiovascular disease and risk man- Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med. 2018;378:270-280. agement: standards of medical care in diabetes-2021. Diabetes Care. [PMID: 29342392] doi:10.1056/NEJMral615295 2021;44:S125-S150. [PMID: 33298421] doi:10.2337/de21-S010

Bibliography Bibliography American Diabetes Association. 10. Cardiovascular disease and risk man- Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med. 2018;378:270-280. agement: standards of medical care in diabetes-2021. Diabetes Care. [PMID: 29342392] doi:10.1056/NEJMral615295 2021;44:S125-S150. [PMID: 33298421] doi:10.2337/de21-S010 w” wo Item 92 Answer: A = Item 93 Answer: E Educational Objective: Diagnose alcoholic = Educational Objective: Prevent recurrent calcium oxa- = ketoacidosis. ws late stone disease. i] The most likely diagnosis is alcoholic ketoacidosis a The most appropriate additional management is to start Ls] (Option A). This patient has an increased anion gap met- wn chlorthalidone (Option E) to decrease urinary calcium ih abolic acidosis with an anion gap of 28, and ketoacidosis a excretion to prevent recurrent calcium oxalate stones. This = due to acute ethanol intoxication is the most likely cause. mr) patient’s urinary calcium excretion is in the high-normal a Alcoholic ketoacidosis occurs in patients following an epi- =< range. The threshold that defines high urinary calcium sode of acute intoxication; however, by the time of clin- excretion and when to initiate a thiazide diuretic for pre- ical evaluation, the ingested ethanol may be extensively vention of calcium oxalate stones is unclear. However, the metabolized, leading to low or absent serum ethanol lev- underlying principle is that the risk for stone formation is els. Ethanol is oxidized to acetaldehyde and then to acetic continuous with increasing amounts of calcium in the urine. acid, during which process the electron-carrier coenzyme Patients with ongoing stone formation despite dietary and nicotinamide adenine dinucleotide (NAD+) is reduced to fluid management should be considered for medical therapy NADH in increasing amounts. Simultaneously, decreased with a thiazide diuretic to decrease urinary calcium excre- insulin secretion (as a result of starvation) and increased tion. Thiazide diuretics can decrease calcium excretion by up counter-regulatory hormones cause lipolysis and genera- to 50% and reduce the recurrence of calcium oxalate stones. tion of ketones, such as acetoacetate and B-hydroxybutyr- Chlorthalidone is the preferred agent because of its long ate, which result in the anion gap. The high ratio of NADH half-life. Chlorthalidone increases calcium reabsorption in to NAD+ leads to increased reduction of acetoacetate to the kidney primarily by causing mild volume depletion, B-hydroxybutyrate. Because the nitroprusside reagent in which increases sodium and calcium reabsorption in the the serum and urine ketone assays detects only acetoace- proximal tubule. When hydrochlorothiazide is used, twice- tate, these tests may be falsely negative due to decreased daily dosing is reeommended. In addition to chlorthalidone, acetoacetate levels despite the presence of increased levels urinary calcium excretion can also be reduced by limiting of the ketone B-hydroxybutyrate, as in this case. Definitive sodium and protein intake. diagnosis may require direct measurement of B-hydroxy- Decreasing calcium intake (Option A) is not the most butyrate levels in the serum, which is available at some appropriate management. Because calcium complexes with laboratories. oxalate in the gastrointestinal tract, decreasing calcium Ethylene glycol and methanol toxicities (Options B, intake allows for increased oxalate absorption and increased D) are associated with a plasma osmolal gap >10 mOsm/kg risk for stone formation. Therefore, unless a person is on H,O. The plasma osmolal gap is calculated as the difference a high-calcium diet (>1500 mg/d), intake should not be between the measured osmolality and calculated osmolality, limited. which is determined as follows: There is no evidence that excess coffee intake is associ- 2 x Serum Sodium (mEq/L) + Plasma Glucose ated with kidney stone disease, so reduction in coffee intake (mg/dL)/18 + Blood Urea Nitrogen (mg/dL)/2.8 (Option B) would not be expected to be beneficial. In this case, the difference between the calculated and Except in patients with hyperoxaluria, limiting oxa- measured osmolality is 3 mOsm/kg H,O (293 mOsm/kg late intake (Option C) has not been shown to decrease the H,O - 290 mOsm/kg H,O), making either ethylene glycol or incidence of stones, and thus the patient does not need to methanol toxicity unlikely. decrease intake. Because isopropyl alcohol (Option C) is metabolized to Because uric acid may serve as a nidus for stone forma- acetone (a ketone), it will lead to ketosis but not to an acido- tion, allopurinol (Option D) has been used to reduce stone sis. An osmolal gap, which is not present in this patient, will occurrence, especially in patients with high levels of uric also develop with isopropyl alcohol intake. acid in the urine, which is not present in this patient.

w” wo Item 92 Answer: A = Item 93 Answer: E Educational Objective: Diagnose alcoholic = Educational Objective: Prevent recurrent calcium oxa- = ketoacidosis. ws late stone disease. i] The most likely diagnosis is alcoholic ketoacidosis a The most appropriate additional management is to start Ls] (Option A). This patient has an increased anion gap met- wn chlorthalidone (Option E) to decrease urinary calcium ih abolic acidosis with an anion gap of 28, and ketoacidosis a excretion to prevent recurrent calcium oxalate stones. This = due to acute ethanol intoxication is the most likely cause. mr) patient’s urinary calcium excretion is in the high-normal a Alcoholic ketoacidosis occurs in patients following an epi- =< range. The threshold that defines high urinary calcium sode of acute intoxication; however, by the time of clin- excretion and when to initiate a thiazide diuretic for pre- ical evaluation, the ingested ethanol may be extensively vention of calcium oxalate stones is unclear. However, the metabolized, leading to low or absent serum ethanol lev- underlying principle is that the risk for stone formation is els. Ethanol is oxidized to acetaldehyde and then to acetic continuous with increasing amounts of calcium in the urine. acid, during which process the electron-carrier coenzyme Patients with ongoing stone formation despite dietary and nicotinamide adenine dinucleotide (NAD+) is reduced to fluid management should be considered for medical therapy NADH in increasing amounts. Simultaneously, decreased with a thiazide diuretic to decrease urinary calcium excre- insulin secretion (as a result of starvation) and increased tion. Thiazide diuretics can decrease calcium excretion by up counter-regulatory hormones cause lipolysis and genera- to 50% and reduce the recurrence of calcium oxalate stones. tion of ketones, such as acetoacetate and B-hydroxybutyr- Chlorthalidone is the preferred agent because of its long ate, which result in the anion gap. The high ratio of NADH half-life. Chlorthalidone increases calcium reabsorption in to NAD+ leads to increased reduction of acetoacetate to the kidney primarily by causing mild volume depletion, B-hydroxybutyrate. Because the nitroprusside reagent in which increases sodium and calcium reabsorption in the the serum and urine ketone assays detects only acetoace- proximal tubule. When hydrochlorothiazide is used, twice- tate, these tests may be falsely negative due to decreased daily dosing is reeommended. In addition to chlorthalidone, acetoacetate levels despite the presence of increased levels urinary calcium excretion can also be reduced by limiting of the ketone B-hydroxybutyrate, as in this case. Definitive sodium and protein intake. diagnosis may require direct measurement of B-hydroxy- Decreasing calcium intake (Option A) is not the most butyrate levels in the serum, which is available at some appropriate management. Because calcium complexes with laboratories. oxalate in the gastrointestinal tract, decreasing calcium Ethylene glycol and methanol toxicities (Options B, intake allows for increased oxalate absorption and increased D) are associated with a plasma osmolal gap >10 mOsm/kg risk for stone formation. Therefore, unless a person is on H,O. The plasma osmolal gap is calculated as the difference a high-calcium diet (>1500 mg/d), intake should not be between the measured osmolality and calculated osmolality, limited. which is determined as follows: There is no evidence that excess coffee intake is associ- 2 x Serum Sodium (mEq/L) + Plasma Glucose ated with kidney stone disease, so reduction in coffee intake (mg/dL)/18 + Blood Urea Nitrogen (mg/dL)/2.8 (Option B) would not be expected to be beneficial. In this case, the difference between the calculated and Except in patients with hyperoxaluria, limiting oxa- measured osmolality is 3 mOsm/kg H,O (293 mOsm/kg late intake (Option C) has not been shown to decrease the H,O - 290 mOsm/kg H,O), making either ethylene glycol or incidence of stones, and thus the patient does not need to methanol toxicity unlikely. decrease intake. Because isopropyl alcohol (Option C) is metabolized to Because uric acid may serve as a nidus for stone forma- acetone (a ketone), it will lead to ketosis but not to an acido- tion, allopurinol (Option D) has been used to reduce stone sis. An osmolal gap, which is not present in this patient, will occurrence, especially in patients with high levels of uric also develop with isopropyl alcohol intake. acid in the urine, which is not present in this patient. 167

Answers and Critiques - — Bibliography van Loon IN, Goto NA, Boereboom FT], et al. Quality of life after the initia- ¢ Thiazide diuretics decrease calcium excretion by up to tion of dialysis or maximal conservative management in elderly patients: 50% and can be used to manage recurrent calcium a longitudinal analysis of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study. BMC Nephrol. 2019;20:108. [PMID: oxalate kidney stones. 30922246] doi:10.1186/s12882-019-1268-3 e In patients with recurrent calcium oxalate kidney stones, urinary calcium excretion can be reduced by limiting sodium and protein intake. Item 95 Answer: A

Bibliography van Loon IN, Goto NA, Boereboom FT], et al. Quality of life after the initia- ¢ Thiazide diuretics decrease calcium excretion by up to tion of dialysis or maximal conservative management in elderly patients: 50% and can be used to manage recurrent calcium a longitudinal analysis of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study. BMC Nephrol. 2019;20:108. [PMID: oxalate kidney stones. 30922246] doi:10.1186/s12882-019-1268-3 e In patients with recurrent calcium oxalate kidney stones, urinary calcium excretion can be reduced by limiting sodium and protein intake. Item 95 Answer: A Educational Objective: Screen for urothelial cancer in a Bibliography patient with hematuria and aristolochic acid nephropathy. Zisman AL. Effectiveness of treatment modalities on kidney stone recur- rence. Clin J Am Soc Nephrol. 2017;12:1699-1708. [PMID: 28830863] Cystoscopy with retrograde pyelography (Option A) is the doi:10.2215/CJN.11201016 most appropriate management for this patient to assess = = for evidence of urothelial tumor. Chronic tubulointerstitial 17.) = nephritis (CTIN) in the setting of protracted use of herbal @O medications, particularly those of Chinese origin, suggests = wn Item 94 Answer: C r+) the possibility of aristolochic acid nephropathy. Consequently, = Educational Objective: Manage end-stage kidney dis- this patient may be at increased risk for urothelial cancer a ease with non-dialytic palliative therapy. (=) despite her young age. CT of the abdomen and pelvis is not se The most appropriate management is to intensify hyper- sufficiently sensitive to rule out neoplasia of the ureters or — x = | bladder. < tension management (Option C). Treatment options for @ patients with end-stage kidney disease (ESKD) include dial- MRI of the kidneys (Option B) is not the most wn

Educational Objective: Screen for urothelial cancer in a Bibliography patient with hematuria and aristolochic acid nephropathy. Zisman AL. Effectiveness of treatment modalities on kidney stone recur- rence. Clin J Am Soc Nephrol. 2017;12:1699-1708. [PMID: 28830863] Cystoscopy with retrograde pyelography (Option A) is the doi:10.2215/CJN.11201016 most appropriate management for this patient to assess = = for evidence of urothelial tumor. Chronic tubulointerstitial 17.) = nephritis (CTIN) in the setting of protracted use of herbal @O medications, particularly those of Chinese origin, suggests = wn Item 94 Answer: C r+) the possibility of aristolochic acid nephropathy. Consequently, = Educational Objective: Manage end-stage kidney dis- this patient may be at increased risk for urothelial cancer a ease with non-dialytic palliative therapy. (=) despite her young age. CT of the abdomen and pelvis is not se The most appropriate management is to intensify hyper- sufficiently sensitive to rule out neoplasia of the ureters or — x = | bladder. < tension management (Option C). Treatment options for @ patients with end-stage kidney disease (ESKD) include dial- MRI of the kidneys (Option B) is not the most wn ysis, transplantation, and the less aggressive option of non- appropriate test for evaluating the lower urinary tract. dialytic medical management only. Shared decision-making Although an MRI may be ordered as an alternative imag-

Educational Objective: Screen for urothelial cancer in a Bibliography patient with hematuria and aristolochic acid nephropathy. Zisman AL. Effectiveness of treatment modalities on kidney stone recur- rence. Clin J Am Soc Nephrol. 2017;12:1699-1708. [PMID: 28830863] Cystoscopy with retrograde pyelography (Option A) is the doi:10.2215/CJN.11201016 most appropriate management for this patient to assess = = for evidence of urothelial tumor. Chronic tubulointerstitial 17.) = nephritis (CTIN) in the setting of protracted use of herbal @O medications, particularly those of Chinese origin, suggests = wn Item 94 Answer: C r+) the possibility of aristolochic acid nephropathy. Consequently, = Educational Objective: Manage end-stage kidney dis- this patient may be at increased risk for urothelial cancer a ease with non-dialytic palliative therapy. (=) despite her young age. CT of the abdomen and pelvis is not se The most appropriate management is to intensify hyper- sufficiently sensitive to rule out neoplasia of the ureters or — x = | bladder. < tension management (Option C). Treatment options for @ patients with end-stage kidney disease (ESKD) include dial- MRI of the kidneys (Option B) is not the most wn ysis, transplantation, and the less aggressive option of non- appropriate test for evaluating the lower urinary tract. dialytic medical management only. Shared decision-making Although an MRI may be ordered as an alternative imag- is vital with these patients. This patient reached an informed ing modality in evaluating for renal masses, CT remains

ysis, transplantation, and the less aggressive option of non- appropriate test for evaluating the lower urinary tract. dialytic medical management only. Shared decision-making Although an MRI may be ordered as an alternative imag- is vital with these patients. This patient reached an informed ing modality in evaluating for renal masses, CT remains decision to pursue non-dialytic medical management. This the gold standard. management is particularly appropriate for older patients Renal angiography (Option C) may be considered for with ESKD and comorbid conditions who may gain only persistent gross hematuria of uncertain etiology when all minimal, if any, additional lifespan. Non-dialytic medical other lower urinary tract imaging modalities have failed to therapy avoids the burdens of dialysis and is associated with identify a cause, but it would not be the most appropriate fewer hospitalizations compared with older patients who management in this case. initiate hemodialysis. The goal of medical management is In a young patient without risk factors for urothelial to prolong the comfort and functioning of a patient’s life cancer (such as smoking, occupational exposure, use of through ongoing medical management of medical problems. Chinese herbal medications), exclusion of stone, renal mass, The appropriate intervention for this patient is to intensify and active urinary tract infections followed by expectant her hypertension management, as she has a history of stroke observation (Option D) is appropriate for a single episode of and her blood pressure is 160/72 mm Hg. Blood pressure gross hematuria. This patient’s analgesic use is relatively low recommendations differ for older patients, but reduction to ascribe the CTIN to this etiology with confidence. There is of systolic blood pressure to <140 mm Hg in patients with no history of occupational or other environmental exposure, stroke is generally supported. and there is no test available to identify aristolochic acid as

recommendations differ for older patients, but reduction to ascribe the CTIN to this etiology with confidence. There is of systolic blood pressure to <140 mm Hg in patients with no history of occupational or other environmental exposure, stroke is generally supported. and there is no test available to identify aristolochic acid as Adding a phosphate binder (Option A) is not appropri- the cause of this patient’s CTIN. However, given the patient’s ate management, as her serum phosphorus level is in the history of protracted use of herbal medications, it would be normal range. prudent to rule out the associated risks of herbal medication Discontinuing all medications other use, such as urothelial tumor. than insu- lin (Option B) in not compatible with the philosophy of non-dialytic medical management, which includes ongoing ¢ Certain Chinese herbal medications have been associ- medical management of medical problems. ated with aristolochic acid nephropathy, which can This patient functions well in her life and has no partic- ular needs that will be met with hospice care. Hospice refer- cause chronic tubulointerstitial disease and is associ- ral (Option D) may be indicated in the future as her chronic ated with urothelial cancer.

Discontinuing all medications other use, such as urothelial tumor. than insu- lin (Option B) in not compatible with the philosophy of non-dialytic medical management, which includes ongoing ¢ Certain Chinese herbal medications have been associ- medical management of medical problems. ated with aristolochic acid nephropathy, which can This patient functions well in her life and has no partic- ular needs that will be met with hospice care. Hospice refer- cause chronic tubulointerstitial disease and is associ- ral (Option D) may be indicated in the future as her chronic ated with urothelial cancer. kidney disease progresses. ¢ CT urography and cystoscopy with retrograde pyelog- raphy are the most appropriate tests for a patient with hematuria and risk factors for urothelial cancer. ¢ The goal of non-dialytic palliative therapy in patients with end-stage kidney disease involves ongoing medi- Bibliography cal management of medical problems to prolong com- Jelakovic B, Dika Z, Arlt VM, et al. Balkan endemic nephropathy and the fort and functioning. causative role of aristolochic acid. Semin Nephrol. 2019;39:284-296. [PMID: 31054628] doi: 10.1016/j.semnephrol.2019.02.007 168

Answers and Critiques C] Item 96 Answer: C end-organ damage. End-organ involvement that meet the diagnostic criteria for preeclampsia includes thrombocy- Educational Objective: Treat infection-related glomer- topenia (platelet count <100,000/uL [100 x 10°/L]); kidney ulonephritis. dysfunction (serum creatinine >1.1 mg/dL [97.2 umol/L]) Continuing nafcillin (Option C) is the most appropriate treat- or a doubling of the serum creatinine concentration); ment for this patient with infection-related glomerulonephri- impaired liver function (elevated aminotransaminases tis (IRGN). IRGN results from a recently resolved infection or levels to >2 times the upper limit of normal); pulmonary an ongoing infection at the time of development of glomeru- edema; and cerebral or visual symptoms such new-onset lonephritis. Diabetes mellitus is the most common comorbid- headache unresponsive to medication and not accounted ity, and older age (+65 years) is a key risk factor; both factors for by alternative diagnoses. In this patient, hypertension, are present in this patient. Treatment of IRGN is typically kidney dysfunction, and new-onset headache are present. supportive and aimed at the infectious etiology. Acute fatty liver of pregnancy (AFP) (Option A) is a rare The prognosis for complete recovery from IRGN is excel- but serious condition that also occurs late in pregnancy. It wv cf} lent in children. However, in adults, the prognosis of the presents with symptoms similar to those of HELLP (hemo- 3

C] Item 96 Answer: C end-organ damage. End-organ involvement that meet the diagnostic criteria for preeclampsia includes thrombocy- Educational Objective: Treat infection-related glomer- topenia (platelet count <100,000/uL [100 x 10°/L]); kidney ulonephritis. dysfunction (serum creatinine >1.1 mg/dL [97.2 umol/L]) Continuing nafcillin (Option C) is the most appropriate treat- or a doubling of the serum creatinine concentration); ment for this patient with infection-related glomerulonephri- impaired liver function (elevated aminotransaminases tis (IRGN). IRGN results from a recently resolved infection or levels to >2 times the upper limit of normal); pulmonary an ongoing infection at the time of development of glomeru- edema; and cerebral or visual symptoms such new-onset lonephritis. Diabetes mellitus is the most common comorbid- headache unresponsive to medication and not accounted ity, and older age (+65 years) is a key risk factor; both factors for by alternative diagnoses. In this patient, hypertension, are present in this patient. Treatment of IRGN is typically kidney dysfunction, and new-onset headache are present. supportive and aimed at the infectious etiology. Acute fatty liver of pregnancy (AFP) (Option A) is a rare The prognosis for complete recovery from IRGN is excel- but serious condition that also occurs late in pregnancy. It wv cf} lent in children. However, in adults, the prognosis of the presents with symptoms similar to those of HELLP (hemo- 3 newly recognized forms of IRGN (e.g., due to Staphylococ- lysis, elevated liver enzymes, and low platelets) syndrome. = cus aureus and gram-negative organisms) is less favorable, ‘= Indicators of liver failure, including hypoglycemia and coag- rs) with more patients developing severe kidney dysfunction, ulopathy, are often worse in AFP than in HELLP syndrome. a) s progressing to chronic kidney disease (CKD) and sometimes This patient has no manifestations of AFP. oc

newly recognized forms of IRGN (e.g., due to Staphylococ- lysis, elevated liver enzymes, and low platelets) syndrome. = cus aureus and gram-negative organisms) is less favorable, ‘= Indicators of liver failure, including hypoglycemia and coag- rs) with more patients developing severe kidney dysfunction, ulopathy, are often worse in AFP than in HELLP syndrome. a) s progressing to chronic kidney disease (CKD) and sometimes This patient has no manifestations of AFP. oc to end-stage kidney disease. Initiation of an ACE inhibitor International Headache Society criteria for migraine wv all o such as lisinopril (Option A) at the time of acute kidney (Option B) without aura include at least five headache = injury is not recommended. However, in this patient's long- attacks lasting 4 to 72 hours; at least four migraine char- wn = term follow-up, lisinopril therapy is a reasonable option if he acteristics (unilateral location, pulsating quality, inhibits <

to end-stage kidney disease. Initiation of an ACE inhibitor International Headache Society criteria for migraine wv all o such as lisinopril (Option A) at the time of acute kidney (Option B) without aura include at least five headache = injury is not recommended. However, in this patient's long- attacks lasting 4 to 72 hours; at least four migraine char- wn = term follow-up, lisinopril therapy is a reasonable option if he acteristics (unilateral location, pulsating quality, inhibits < develops proteinuric CKD as a residual of IRGN. or prohibits daily activities, aggravation by walking up or Adding a trial of glucocorticoid therapy such as predni- down stairs or similar routine physical activity); and at least sone (Option B) to antibiotic therapy for IRGN is considered one associated symptom (nausea/vomiting, photophobia/ only in rare cases in which a severe proliferative glomerulo- phonophobia). In addition, the headache cannot be better nephritis on biopsy is accompanied by a rapid progression accounted for by another diagnosis. Preeclampsia is a better toward kidney failure. In this patient, the glomerular lesion explanation for this patient’s headache. is not described as severe, and his serum creatinine levels Hypertension associated with pheochromocytoma during his hospitalization do not indicate rapidly progressive (Option C) can showa sustained pattern, with or without par- glomerulonephritis defined by at least a 50% decline in glo- oxysms, or occur as paroxysms only. Pheochromocytoma is merular filtration rate over a short time period. rare and typically associated with additional findings (tachy- The indication for diuretics and sodium restriction is cardia, nervousness, diaphoresis). Proteinuria and acute ele- the presence of hypertension and edema secondary to fluid vation of serum creatinine are not typical manifestations. retention. In these cases, sodium restriction and a loop diuretic (Option D) are recommended first-line therapies. Because this patient does not have evidence of hypertension e Preeclampsia is defined as new-onset hypertension or edema, these therapies are not indicated. with proteinuria (=300 mg/24 h or a urine protein- creatinine ratio >300 mg/g) after 20 weeks of pregnancy.

develops proteinuric CKD as a residual of IRGN. or prohibits daily activities, aggravation by walking up or Adding a trial of glucocorticoid therapy such as predni- down stairs or similar routine physical activity); and at least sone (Option B) to antibiotic therapy for IRGN is considered one associated symptom (nausea/vomiting, photophobia/ only in rare cases in which a severe proliferative glomerulo- phonophobia). In addition, the headache cannot be better nephritis on biopsy is accompanied by a rapid progression accounted for by another diagnosis. Preeclampsia is a better toward kidney failure. In this patient, the glomerular lesion explanation for this patient’s headache. is not described as severe, and his serum creatinine levels Hypertension associated with pheochromocytoma during his hospitalization do not indicate rapidly progressive (Option C) can showa sustained pattern, with or without par- glomerulonephritis defined by at least a 50% decline in glo- oxysms, or occur as paroxysms only. Pheochromocytoma is merular filtration rate over a short time period. rare and typically associated with additional findings (tachy- The indication for diuretics and sodium restriction is cardia, nervousness, diaphoresis). Proteinuria and acute ele- the presence of hypertension and edema secondary to fluid vation of serum creatinine are not typical manifestations. retention. In these cases, sodium restriction and a loop diuretic (Option D) are recommended first-line therapies. Because this patient does not have evidence of hypertension e Preeclampsia is defined as new-onset hypertension or edema, these therapies are not indicated. with proteinuria (=300 mg/24 h or a urine protein- creatinine ratio >300 mg/g) after 20 weeks of pregnancy. e Preeclampsia can be diagnosed in pregnant patients e Treatment of infection-related glomerulonephritis is without proteinuria if hypertension is accompanied typically supportive and aimed at the infectious etiology. by evidence of other end-organ damage (thrombocy- topenia, kidney dysfunction, liver dysfunction, pul- Bibliography monary edema, cerebral or visual symptoms). Nasr SH, Radhakrishnan J, D’Agati VD. Bacterial infection-related glomeru- lonephritis in adults. Kidney Int. 2013;83:792-803. [PMID: 23302723] doi:10.1038/ki.2012.407 Bibliography American College of Obstetricians and Gynecologists. Practice Bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol. 2019; 133:e1-e25. [PMID: 30575675] Item 97 Answer: D Educational Objective: Diagnose preeclampsia. Item 98 Answer: D The most likely diagnosis is preeclampsia (Option D). Educational Objective: Evaluate kidney function with Preeclampsia is defined as new-onset hypertension with serum cystatin C measurement. proteinuria (>300 mg/24 h or a urine protein-creatinine ratio >300 mg/g) after 20 weeks of pregnancy. Preeclamp- The most appropriate test is serum cystatin C measurement sia can also be diagnosed in patients without proteinuria (Option D). Reduction of muscle mass, as seen in amputees if the hypertension is accompanied by evidence of other and those with malnutrition or muscle wasting, can result in

e Preeclampsia can be diagnosed in pregnant patients e Treatment of infection-related glomerulonephritis is without proteinuria if hypertension is accompanied typically supportive and aimed at the infectious etiology. by evidence of other end-organ damage (thrombocy- topenia, kidney dysfunction, liver dysfunction, pul- Bibliography monary edema, cerebral or visual symptoms). Nasr SH, Radhakrishnan J, D’Agati VD. Bacterial infection-related glomeru- lonephritis in adults. Kidney Int. 2013;83:792-803. [PMID: 23302723] doi:10.1038/ki.2012.407 Bibliography American College of Obstetricians and Gynecologists. Practice Bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol. 2019; 133:e1-e25. [PMID: 30575675] Item 97 Answer: D Educational Objective: Diagnose preeclampsia. Item 98 Answer: D The most likely diagnosis is preeclampsia (Option D). Educational Objective: Evaluate kidney function with Preeclampsia is defined as new-onset hypertension with serum cystatin C measurement. proteinuria (>300 mg/24 h or a urine protein-creatinine ratio >300 mg/g) after 20 weeks of pregnancy. Preeclamp- The most appropriate test is serum cystatin C measurement sia can also be diagnosed in patients without proteinuria (Option D). Reduction of muscle mass, as seen in amputees if the hypertension is accompanied by evidence of other and those with malnutrition or muscle wasting, can result in 169

Dewees ariel Betis a lower serum creatinine concentration without a change in birefringence with Congo red stain when kidney biopsy glomerular filtration rate (GFR). Because of decreased muscle specimens are examined under polarized light. The most mass, serum creatinine overestimates kidney function in older common form of renal amyloidosis, occurring in 60% to persons, especially women. Young persons and men often have 65% of patients, is derived from monoclonal immunoglob- higher muscle mass and higher serum creatinine concentration ulin light chains (AL amyloid, as in this case). Amyloidosis at a given GFR compared with older persons and thus under- may be confined to one organ or affect multiple organs; estimates kidney function in this population. This patient’s kidney involvement is common in systemic amyloidosis. AL elevated serum creatinine level is likely the result of increased amyloidosis typically affects patients >50 years of age, pre- muscle mass. Serum cystatin C is an alternative marker of GFR dominantly men. When kidney involvement occurs, patients that is less influenced than serum creatinine by age, sex, muscle typically present with nephrotic-range proteinuria (with the mass, and body weight. Cystatin C is produced by all nucleated full nephrotic syndrome seen in 25% to 50% of patients) as cells, completely filtered by glomeruli, and then metabolized well as some degree of renal insufficiency. Serum and urine > by renal tubules; serum levels thus provide an index of GFR. protein electrophoresis with immunofixation can identify 3 7) Serum cystatin C is more sensitive in identifying milder decre- the monoclonal protein, but quantification of serum free light = ments in kidney function than serum creatinine. chains («, 4) provides a more sensitive assay. In practice, all © a Blood urea nitrogen (BUN) (Option A) is derived from three testing modalities are usually checked simultaneously. gy = the metabolism of proteins. BUN concentration is a poor Diabetic kidney disease (Option A) typically occurs after 2. marker of kidney function because it is not produced at a long-standing type 2 diabetes mellitus (typically >10 years’ a) = constant rate and is reabsorbed along the tubules; further- duration) in patients with other evidence of microvascular =. more, alterations in renal blood flow markedly influence or macrovascular complications of disease, most notably 2 = tubular reabsorption and excretion. diabetic retinopathy, which this patient did not have. In the o wn Because of the secretion of creatinine in the proxi- absence of these characteristic findings, a kidney biopsy mal tubule, the direct measurement of creatinine clearance should be performed to establish a diagnosis. (Option B) with a 24-hour urine collection tends to over- IgA nephropathy (IgAN) (Option B) is the most common estimate GFR. Nonetheless, with an adequate collection, primary glomerular disease worldwide, usually diagnosed in the 24-hour urine collection can be used to estimate GFR; youth or early adulthood. IgAN can present with any of the however, this test is prone to collection errors and would be manifestations of the nephritic syndrome. Diagnosis may be unnecessarily burdensome for this patient. suspected clinically but can only be made by kidney biopsy Radionuclide imaging (Option C) provides the most showing dominant mesangial immune deposits of IgA with accurate measurement of GFR and is the gold standard in C3, and occasionally IgG or IgM. This older patient present- research. It is useful for accurate determination of GFR ing with the nephrotic syndrome is not compatible with the during evaluation of kidney donors, evaluation of recipients diagnosis of IgAN. for other organs, or assessment of the differential GFR of Patients with membranous nephropathy (Option C) typi- each kidney before nephrectomy. However, for this patient, cally describe slowly progressive edema, and laboratory testing the availability of serum cystatin C measurement makes reveals proteinuria, hypoalbuminemia, and hyperlipidemia, radionuclide imaging unnecessary. most often with preserved kidney function. Diagnosis is tra- ditionally made by kidney biopsy, although serologic testing for anti-phospholipase A2 receptor antibodies allows for the e Increased or decreased muscle mass can alter the possibility of diagnosing the disease noninvasively. The hallmark serum creatinine level in the absence of kidney disease. biopsy finding is the presence of subepithelial immune deposits. e Serum cystatin C is more sensitive in identifying milder decrements in kidney function than serum e The gold standard for pathologic diagnosis of amyloido- creatinine. sis is the characteristic apple-green birefringence with Congo red stain when examined under polarized light. Bibliography Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Bibliography Clin J Am Soc Nephrol. 2008;3:348-354. [PMID: 18235143] doi:10.2215/ Hogan JJ, Alexander MP, Leung N. Dysproteinemia and the kidney: core cur- CJN.02870707 riculum 2019. Am J Kidney Dis. 2019;74:822-836. [PMID: 31331759] doi:10.1053/j.ajkd.2019.04.029

a lower serum creatinine concentration without a change in birefringence with Congo red stain when kidney biopsy glomerular filtration rate (GFR). Because of decreased muscle specimens are examined under polarized light. The most mass, serum creatinine overestimates kidney function in older common form of renal amyloidosis, occurring in 60% to persons, especially women. Young persons and men often have 65% of patients, is derived from monoclonal immunoglob- higher muscle mass and higher serum creatinine concentration ulin light chains (AL amyloid, as in this case). Amyloidosis at a given GFR compared with older persons and thus under- may be confined to one organ or affect multiple organs; estimates kidney function in this population. This patient’s kidney involvement is common in systemic amyloidosis. AL elevated serum creatinine level is likely the result of increased amyloidosis typically affects patients >50 years of age, pre- muscle mass. Serum cystatin C is an alternative marker of GFR dominantly men. When kidney involvement occurs, patients that is less influenced than serum creatinine by age, sex, muscle typically present with nephrotic-range proteinuria (with the mass, and body weight. Cystatin C is produced by all nucleated full nephrotic syndrome seen in 25% to 50% of patients) as cells, completely filtered by glomeruli, and then metabolized well as some degree of renal insufficiency. Serum and urine > by renal tubules; serum levels thus provide an index of GFR. protein electrophoresis with immunofixation can identify 3 7) Serum cystatin C is more sensitive in identifying milder decre- the monoclonal protein, but quantification of serum free light = ments in kidney function than serum creatinine. chains («, 4) provides a more sensitive assay. In practice, all © a Blood urea nitrogen (BUN) (Option A) is derived from three testing modalities are usually checked simultaneously. gy = the metabolism of proteins. BUN concentration is a poor Diabetic kidney disease (Option A) typically occurs after 2. marker of kidney function because it is not produced at a long-standing type 2 diabetes mellitus (typically >10 years’ a) = constant rate and is reabsorbed along the tubules; further- duration) in patients with other evidence of microvascular =. more, alterations in renal blood flow markedly influence or macrovascular complications of disease, most notably 2 = tubular reabsorption and excretion. diabetic retinopathy, which this patient did not have. In the o wn Because of the secretion of creatinine in the proxi- absence of these characteristic findings, a kidney biopsy mal tubule, the direct measurement of creatinine clearance should be performed to establish a diagnosis. (Option B) with a 24-hour urine collection tends to over- IgA nephropathy (IgAN) (Option B) is the most common estimate GFR. Nonetheless, with an adequate collection, primary glomerular disease worldwide, usually diagnosed in the 24-hour urine collection can be used to estimate GFR; youth or early adulthood. IgAN can present with any of the however, this test is prone to collection errors and would be manifestations of the nephritic syndrome. Diagnosis may be unnecessarily burdensome for this patient. suspected clinically but can only be made by kidney biopsy Radionuclide imaging (Option C) provides the most showing dominant mesangial immune deposits of IgA with accurate measurement of GFR and is the gold standard in C3, and occasionally IgG or IgM. This older patient present- research. It is useful for accurate determination of GFR ing with the nephrotic syndrome is not compatible with the during evaluation of kidney donors, evaluation of recipients diagnosis of IgAN. for other organs, or assessment of the differential GFR of Patients with membranous nephropathy (Option C) typi- each kidney before nephrectomy. However, for this patient, cally describe slowly progressive edema, and laboratory testing the availability of serum cystatin C measurement makes reveals proteinuria, hypoalbuminemia, and hyperlipidemia, radionuclide imaging unnecessary. most often with preserved kidney function. Diagnosis is tra- ditionally made by kidney biopsy, although serologic testing for anti-phospholipase A2 receptor antibodies allows for the e Increased or decreased muscle mass can alter the possibility of diagnosing the disease noninvasively. The hallmark serum creatinine level in the absence of kidney disease. biopsy finding is the presence of subepithelial immune deposits. e Serum cystatin C is more sensitive in identifying milder decrements in kidney function than serum e The gold standard for pathologic diagnosis of amyloido- creatinine. sis is the characteristic apple-green birefringence with Congo red stain when examined under polarized light. Bibliography Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Bibliography Clin J Am Soc Nephrol. 2008;3:348-354. [PMID: 18235143] doi:10.2215/ Hogan JJ, Alexander MP, Leung N. Dysproteinemia and the kidney: core cur- CJN.02870707 riculum 2019. Am J Kidney Dis. 2019;74:822-836. [PMID: 31331759] doi:10.1053/j.ajkd.2019.04.029 Item 99 Answer: D Educational Objective: Diagnose renal AL amyloidosis. Item 100 Answer: D Educational Objective: Diagnose minimal change Renal AL amyloidosis (Option D) is the most likely diagnosis glomerulopathy with acute kidney injury. in this patient. Amyloidosis is characterized by extracellular tissue deposition of fibrillary protein. The gold standard The most likely diagnosis is minimal change glomerulopathy for pathologic diagnosis is the characteristic apple-green (MCG; also known as minimal change disease) (Option D) in

Item 99 Answer: D Educational Objective: Diagnose renal AL amyloidosis. Item 100 Answer: D Educational Objective: Diagnose minimal change Renal AL amyloidosis (Option D) is the most likely diagnosis glomerulopathy with acute kidney injury. in this patient. Amyloidosis is characterized by extracellular tissue deposition of fibrillary protein. The gold standard The most likely diagnosis is minimal change glomerulopathy for pathologic diagnosis is the characteristic apple-green (MCG; also known as minimal change disease) (Option D) in 170

this older patient who has the nephrotic syndrome with acute thinning suggest advanced chronic kidney disease. Patients kidney injury (AKI). MCG is the most common cause of the with ESKD and advanced age or multiple comorbidities may nephrotic syndrome in children (+90% of cases), but it is also not want renal replacement therapy. For these patients, pal- responsible for 10% to 15% of cases of the nephrotic syndrome liative care aimed at improving the quality of life may be a in adults, especially older patients (=65 years of age) and better option. Such care aligns treatment with a patient's elderly patients (280 years of age). The classic presentation goals through culturally sensitive shared decision-making of MCG is sudden-onset nephrotic syndrome with abrupt and advance care planning, along with treating symptoms appearance of edema and, eventually, anasarca. Up to 25% of resulting from uremia, hypervolemia, hyperkalemia, and/or adults with MCG may also have AKI, with an increased risk in acidosis. Therefore, a discussion of overall goals of care is the older patients with hypertension, low serum albumin levels, most appropriate next step. and heavy proteinuria. Another cause of the nephrotic syn- Initiating intravenous 0.9% saline (Option B) is not an drome with AKI includes MCG with concomitant interstitial appropriate management step. The patient does not appear nephritis in the setting of NSAID use and collapsing forms of hypovolemic, and volume expansion will not help. wn a focal segmental glomerulosclerosis. In patients with obstructive uropathy, noncontrast CT of s Both ANCA-associated glomerulonephritis and anti- the abdomen and pelvis (Option C) is indicated for suspected = glomerular basement membrane antibody disease (Options nephrolithiasis. The patient’s finding of persistent hydro- = Oo A, B) can cause severe AKI in an elderly patient, but the nephrosis on repeat kidney ultrasound is not unusual in = urinary findings in these rapidly progressive glomerulo- =] patients a few days following relief of long-standing obstruc- o nephritides show both hematuria and subnephrotic-range tion and does not indicate the presence of bilateral ureteral wn coal

this older patient who has the nephrotic syndrome with acute thinning suggest advanced chronic kidney disease. Patients kidney injury (AKI). MCG is the most common cause of the with ESKD and advanced age or multiple comorbidities may nephrotic syndrome in children (+90% of cases), but it is also not want renal replacement therapy. For these patients, pal- responsible for 10% to 15% of cases of the nephrotic syndrome liative care aimed at improving the quality of life may be a in adults, especially older patients (=65 years of age) and better option. Such care aligns treatment with a patient's elderly patients (280 years of age). The classic presentation goals through culturally sensitive shared decision-making of MCG is sudden-onset nephrotic syndrome with abrupt and advance care planning, along with treating symptoms appearance of edema and, eventually, anasarca. Up to 25% of resulting from uremia, hypervolemia, hyperkalemia, and/or adults with MCG may also have AKI, with an increased risk in acidosis. Therefore, a discussion of overall goals of care is the older patients with hypertension, low serum albumin levels, most appropriate next step. and heavy proteinuria. Another cause of the nephrotic syn- Initiating intravenous 0.9% saline (Option B) is not an drome with AKI includes MCG with concomitant interstitial appropriate management step. The patient does not appear nephritis in the setting of NSAID use and collapsing forms of hypovolemic, and volume expansion will not help. wn a focal segmental glomerulosclerosis. In patients with obstructive uropathy, noncontrast CT of s Both ANCA-associated glomerulonephritis and anti- the abdomen and pelvis (Option C) is indicated for suspected = glomerular basement membrane antibody disease (Options nephrolithiasis. The patient’s finding of persistent hydro- = Oo A, B) can cause severe AKI in an elderly patient, but the nephrosis on repeat kidney ultrasound is not unusual in = urinary findings in these rapidly progressive glomerulo- =] patients a few days following relief of long-standing obstruc- o nephritides show both hematuria and subnephrotic-range tion and does not indicate the presence of bilateral ureteral wn coal proteinuria. This patient’s findings on urinalysis are typical o obstruction. Similarly, there is no indication that ureteral = of the nephrotic syndrome, not glomerulonephritis. stents will further improve kidney function (Option D). wn” = Membranous nephropathy (Option C) can also cause =<t the nephrotic syndrome and AKI. However, AKI seen in membranous nephropathy is usually due to renal vein e Long-standing obstructive uropathy may lead to end-

proteinuria. This patient’s findings on urinalysis are typical o obstruction. Similarly, there is no indication that ureteral = of the nephrotic syndrome, not glomerulonephritis. stents will further improve kidney function (Option D). wn” = Membranous nephropathy (Option C) can also cause =<t the nephrotic syndrome and AKI. However, AKI seen in membranous nephropathy is usually due to renal vein e Long-standing obstructive uropathy may lead to end- thrombosis, which was not seen on this patient’s Doppler stage kidney disease even if the source of obstruction ultrasound. Membranous nephropathy is most commonly is corrected. diagnosed in middle-aged adults, with a slight male pre- e Patients with end-stage kidney disease and advanced dominance, and is an unusual etiology of the nephrotic age or multiple comorbidities may not want renal syndrome in patients >75 years of age unless there is an replacement therapy and will benefit from a discus- underlying malignancy. Furthermore, the onset of edema in sion focused on overall goals of care. membranous nephropathy is usually slower than in MCG.

thrombosis, which was not seen on this patient’s Doppler stage kidney disease even if the source of obstruction ultrasound. Membranous nephropathy is most commonly is corrected. diagnosed in middle-aged adults, with a slight male pre- e Patients with end-stage kidney disease and advanced dominance, and is an unusual etiology of the nephrotic age or multiple comorbidities may not want renal syndrome in patients >75 years of age unless there is an replacement therapy and will benefit from a discus- underlying malignancy. Furthermore, the onset of edema in sion focused on overall goals of care. membranous nephropathy is usually slower than in MCG. Bibliography Selius BA, Subedi R. Urinary retention in adults: diagnosis and initial man- ¢ The classic presentation of minimal change glomeru- agement. Am Fam Physician. 2008;77:643-650. [PMID: 18350762] lopathy is sudden-onset nephrotic syndrome with abrupt appearance of edema and, eventually, ana- sarca. Item 102 Answer: D ¢ Up to 25% of adults with minimal change glomerulop- Educational Objective: Treat autosomal dominant poly- athy may have acute kidney injury, with a particular cystic kidney disease with tolvaptan. risk in older patients with hypertension, low serum albumin levels, and heavy proteinuria. The most appropriate treatment for this patient is tolvaptan (Option D). In 2018, tolvaptan was approved by the FDA to Bibliography slow kidney function decline in adults at risk for progressive Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome autosomal dominant polycystic kidney disease (ADPKD). This of minimal change disease. Kidney Int. 2018;94:861-869. [PMID: patient has four known risk factors associated with progres- 29980292] doi:10.1016 /j.kint.2018.04.024 sion to end-stage kidney disease (ESKD): onset of hyperten- sion before 35 years of age; urologic events (gross hematuria, Item 101 Answer: A cyst infection, and/or flank pain) before 35 years of age; an estimated glomerular filtration rate decrease >5 mL/min/ Educational Objective: Manage end-stage kidney disease. 1.73 m? within 1 year; and a family history of ESKD at or The most appropriate next step in management is to discuss before 58 years of age. Other risk factors associated with goals of care (Option A). This patient has end-stage kid- progression to ESKD include male sex, total kidney volume ney disease (ESKD) due to long-standing urinary retention greater than expected for age, and truncating PKDI variant. from prostatic hyperplasia. There is no significant diuresis Before the availability of tolvaptan, blood pressure con- during the 48 hours since bladder catheter placement, and trol using blockade of the renin-aldosterone system was the decrease in his serum creatinine level is insignificant. the only validated therapeutic strategy for management of The small kidney sizes with severe cortical echogenicity and ADPKD. This conservative therapy should still be a staple of

Bibliography Selius BA, Subedi R. Urinary retention in adults: diagnosis and initial man- ¢ The classic presentation of minimal change glomeru- agement. Am Fam Physician. 2008;77:643-650. [PMID: 18350762] lopathy is sudden-onset nephrotic syndrome with abrupt appearance of edema and, eventually, ana- sarca. Item 102 Answer: D ¢ Up to 25% of adults with minimal change glomerulop- Educational Objective: Treat autosomal dominant poly- athy may have acute kidney injury, with a particular cystic kidney disease with tolvaptan. risk in older patients with hypertension, low serum albumin levels, and heavy proteinuria. The most appropriate treatment for this patient is tolvaptan (Option D). In 2018, tolvaptan was approved by the FDA to Bibliography slow kidney function decline in adults at risk for progressive Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome autosomal dominant polycystic kidney disease (ADPKD). This of minimal change disease. Kidney Int. 2018;94:861-869. [PMID: patient has four known risk factors associated with progres- 29980292] doi:10.1016 /j.kint.2018.04.024 sion to end-stage kidney disease (ESKD): onset of hyperten- sion before 35 years of age; urologic events (gross hematuria, Item 101 Answer: A cyst infection, and/or flank pain) before 35 years of age; an estimated glomerular filtration rate decrease >5 mL/min/ Educational Objective: Manage end-stage kidney disease. 1.73 m? within 1 year; and a family history of ESKD at or The most appropriate next step in management is to discuss before 58 years of age. Other risk factors associated with goals of care (Option A). This patient has end-stage kid- progression to ESKD include male sex, total kidney volume ney disease (ESKD) due to long-standing urinary retention greater than expected for age, and truncating PKDI variant. from prostatic hyperplasia. There is no significant diuresis Before the availability of tolvaptan, blood pressure con- during the 48 hours since bladder catheter placement, and trol using blockade of the renin-aldosterone system was the decrease in his serum creatinine level is insignificant. the only validated therapeutic strategy for management of The small kidney sizes with severe cortical echogenicity and ADPKD. This conservative therapy should still be a staple of 171

treating patients with ADPKD, including those on tolvaptan. severe hypertension. The patient also has a metabolic alka- This patient is already taking an ACE inhibitor with blood losis. pressure at goal; she would not be expected to have any ben- Plasma fractionated metanephrines (Option B) are efit from switching to an angiotensin receptor blocker such obtained to screen for a pheochromocytoma. The absence as telmisartan at this point (Option A). of episodic palpitations, headaches, and tachycardia and Measurement of total kidney volume can be important the presence of metabolic alkalosis and hypokalemia make in assessing risk for ESKD in patients with ADPKD; volume pheochromocytomaa less likely diagnosis for this patient. can be compared to expected volume for age, and changes Renal artery CT angiography (Option C) is an appropri- in volume over time can also be assessed. Ultrasonography ate screening test for renovascular disease, including fibro- (Option B) is an acceptable modality for kidney size and muscular dysplasia. Older patients with renovascular hyper- cyst burden but is inferior to MRI for measurement of total tension often have other manifestations of atherosclerosis, kidney volume. This patient, however, does not require a including the presence of coronary artery, cerebrovascular,

treating patients with ADPKD, including those on tolvaptan. severe hypertension. The patient also has a metabolic alka- This patient is already taking an ACE inhibitor with blood losis. pressure at goal; she would not be expected to have any ben- Plasma fractionated metanephrines (Option B) are efit from switching to an angiotensin receptor blocker such obtained to screen for a pheochromocytoma. The absence as telmisartan at this point (Option A). of episodic palpitations, headaches, and tachycardia and Measurement of total kidney volume can be important the presence of metabolic alkalosis and hypokalemia make in assessing risk for ESKD in patients with ADPKD; volume pheochromocytomaa less likely diagnosis for this patient. can be compared to expected volume for age, and changes Renal artery CT angiography (Option C) is an appropri- in volume over time can also be assessed. Ultrasonography ate screening test for renovascular disease, including fibro- (Option B) is an acceptable modality for kidney size and muscular dysplasia. Older patients with renovascular hyper- cyst burden but is inferior to MRI for measurement of total tension often have other manifestations of atherosclerosis, kidney volume. This patient, however, does not require a including the presence of coronary artery, cerebrovascular, > measurement of total kidney volume to be considered high or peripheral vascular disease. Lateralizing abdominal bruits = wn risk given her confluence of other risk factors; she can pro- may be auscultated. Abrupt onset of hypertension in patients = ceed directly to tolvaptan therapy without a kidney volume <35 years of age suggests fibromuscular dysplasia. None of © these clinical findings is present to suggest the diagnosis of —% wn measurement. my bp | Octreotide (Option C) has been shown to reduce kidney renovascular disease. a cyst fluid accumulation in selected patients with ADPKD but The 24-hour urine free cortisol (Option D) is a fre- oO =e has not been shown to slow the decline in kidney function quently used screening test for hypercortisolism. In adults, =. as seen with tolvaptan. hypercortisolism may manifest as hypertension and hypo- <2 < kalemia, but it is relatively rare compared with primary © wn hyperaldosteronism. In the absence of Cushingoid facies, ¢ Tolvaptan can slow kidney function decline in adults central obesity, proximal muscle weakness, and ecchymosis, at risk for progressive autosomal dominant polycystic Cushing syndrome is a very unlikely cause of this patient’s kidney disease. hypertension.

> measurement of total kidney volume to be considered high or peripheral vascular disease. Lateralizing abdominal bruits = wn risk given her confluence of other risk factors; she can pro- may be auscultated. Abrupt onset of hypertension in patients = ceed directly to tolvaptan therapy without a kidney volume <35 years of age suggests fibromuscular dysplasia. None of © these clinical findings is present to suggest the diagnosis of —% wn measurement. my bp | Octreotide (Option C) has been shown to reduce kidney renovascular disease. a cyst fluid accumulation in selected patients with ADPKD but The 24-hour urine free cortisol (Option D) is a fre- oO =e has not been shown to slow the decline in kidney function quently used screening test for hypercortisolism. In adults, =. as seen with tolvaptan. hypercortisolism may manifest as hypertension and hypo- <2 < kalemia, but it is relatively rare compared with primary © wn hyperaldosteronism. In the absence of Cushingoid facies, ¢ Tolvaptan can slow kidney function decline in adults central obesity, proximal muscle weakness, and ecchymosis, at risk for progressive autosomal dominant polycystic Cushing syndrome is a very unlikely cause of this patient’s kidney disease. hypertension. ¢ Blockade of the renin-aldosterone system is a staple of treating patients with autosomal dominant polycystic ¢ Primary hyperaldosteronism is the most common cause kidney disease, including those on tolvaptan. of secondary hypertension and should be suspected in patients with resistant hypertension, hypokalemia, Bibliography family history of early-onset hypertension, blood pres- Chebib FT, Perrone RD, Chapman AB, et al. A practical guide for treatment of rapidly progressive ADPKD with tolvaptan. J Am Soc Nephrol. 2018; sure >160/100 mm Hg, or stroke at age <40 years. 29:2458-2470. [PMID: 30228150] doi:10.1681/ASN.2018060590 ¢ The plasma aldosterone concentration/plasma renin activity ratio is the recommended screening test for Item 103 Answer: A primary hyperaldosteronism.

¢ Blockade of the renin-aldosterone system is a staple of treating patients with autosomal dominant polycystic ¢ Primary hyperaldosteronism is the most common cause kidney disease, including those on tolvaptan. of secondary hypertension and should be suspected in patients with resistant hypertension, hypokalemia, Bibliography family history of early-onset hypertension, blood pres- Chebib FT, Perrone RD, Chapman AB, et al. A practical guide for treatment of rapidly progressive ADPKD with tolvaptan. J Am Soc Nephrol. 2018; sure >160/100 mm Hg, or stroke at age <40 years. 29:2458-2470. [PMID: 30228150] doi:10.1681/ASN.2018060590 ¢ The plasma aldosterone concentration/plasma renin activity ratio is the recommended screening test for Item 103 Answer: A primary hyperaldosteronism. Educational Objective: Diagnose primary hyperaldoste- ronism as a secondary cause of hypertension. Bibliography Lee FT, Elaraj D. Evaluation and management of primary hyperaldosteron- The most appropriate diagnostic test to perform next is the ism. Surg Clin North Am. 2019;99:731-745. [PMID: 31255203] doi:10.1016/j.suc.2019.04.010 plasma aldosterone concentration/plasma renin activity ratio (Option A). Primary hyperaldosteronism, in which aldoste- rone production cannot be suppressed with sodium loading, is Item 104 Answer: A the most common cause of secondary hypertension in middle- Educational Objective: Manage edema associated with aged adults and an important cause of resistant hypertension. the nephrotic syndrome. A triad of resistant hypertension, metabolic alkalosis, and hypokalemia (including in patients treated with low-dose The most appropriate management is to add metolazone thiazide diuretics) should raise suspicion. Screening is recom- (Option A). This patient with the nephrotic syndrome due mended if any of the following are present: resistant hyper- to focal segmental glomerulosclerosis (FSGS) has refractory tension; hypokalemia (spontaneous or substantial, if diuretic edema despite therapy with maximal doses of oral furosemide induced); incidentally discovered adrenal mass; family history and therefore needs additional diuretic therapy. Addition of a of early-onset hypertension; moderately severe hypertension second diuretic that works distal to the loop of Henle, such as (>160/100 mm Hg); or stroke at age <40 years. It is common a thiazide diuretic and/or a potassium-sparing diuretic, is the for patients with primary hyperaldosteronism to have normal appropriate next step in management. In patients taking high- serum potassium levels; a high index of suspicion is therefore dose loop diuretics, increased delivery of salt and water to required. This patient has substantial hypokalemia (serum the distal portions of the nephron can lead to hypertrophy of potassium level of 2.9 mEq/L [2.9 mmol/L]) with initiation these segments and overabsorption of sodium, undermining of low-dose hydrochlorothiazide and persistent, moderately the effects of the loop diuretic.

Educational Objective: Diagnose primary hyperaldoste- ronism as a secondary cause of hypertension. Bibliography Lee FT, Elaraj D. Evaluation and management of primary hyperaldosteron- The most appropriate diagnostic test to perform next is the ism. Surg Clin North Am. 2019;99:731-745. [PMID: 31255203] doi:10.1016/j.suc.2019.04.010 plasma aldosterone concentration/plasma renin activity ratio (Option A). Primary hyperaldosteronism, in which aldoste- rone production cannot be suppressed with sodium loading, is Item 104 Answer: A the most common cause of secondary hypertension in middle- Educational Objective: Manage edema associated with aged adults and an important cause of resistant hypertension. the nephrotic syndrome. A triad of resistant hypertension, metabolic alkalosis, and hypokalemia (including in patients treated with low-dose The most appropriate management is to add metolazone thiazide diuretics) should raise suspicion. Screening is recom- (Option A). This patient with the nephrotic syndrome due mended if any of the following are present: resistant hyper- to focal segmental glomerulosclerosis (FSGS) has refractory tension; hypokalemia (spontaneous or substantial, if diuretic edema despite therapy with maximal doses of oral furosemide induced); incidentally discovered adrenal mass; family history and therefore needs additional diuretic therapy. Addition of a of early-onset hypertension; moderately severe hypertension second diuretic that works distal to the loop of Henle, such as (>160/100 mm Hg); or stroke at age <40 years. It is common a thiazide diuretic and/or a potassium-sparing diuretic, is the for patients with primary hyperaldosteronism to have normal appropriate next step in management. In patients taking high- serum potassium levels; a high index of suspicion is therefore dose loop diuretics, increased delivery of salt and water to required. This patient has substantial hypokalemia (serum the distal portions of the nephron can lead to hypertrophy of potassium level of 2.9 mEq/L [2.9 mmol/L]) with initiation these segments and overabsorption of sodium, undermining of low-dose hydrochlorothiazide and persistent, moderately the effects of the loop diuretic. 172

_ Answers and Critiques Factors that warrant admission for intravenous (IV) nephritis, which can lead to chronic glomerular basement diuretics include lack of response after addition of a thiazide membrane changes but not acute glomerulonephritis. Fur- and/or potassium-sparing diuretic to a loop diuretic; acute thermore, neither acute viral encephalitis nor acyclovir is respiratory symptoms secondary to pulmonary edema; or associated with acute glomerulonephritis. significant ascites that raise concern for gut edema and Acute interstitial nephritis (AIN) (Option B) is a com- malabsorption of oral diuretics. These factors are not present mon cause of AKI and is characterized by inflammation and in this patient. A number of randomized clinical trials have edema of the interstitium. The classic clinical presentation of evaluated the efficacy of a continuous IV infusion of loop fever, rash, and peripheral eosinophilia occurs in only 10% to diuretics compared with IV bolus therapy (Options B, C). 30% of patients with AIN. Drug-induced AIN, especially due Findings indicated that continuous IV infusion is associated to antibiotics, is the most common cause of AIN and should with less ototoxicity than bolus injections of loop diuretics, be considered in any patient with AKI, a characteristic uri- but clear evidence of its diuretic superiority is lacking, at the nalysis, and history of any drug exposure. Drug-induced AIN minimum in heart failure patients. typically takes 7 to 10 days to develop and is characterized by w a This patient’s significant edema alongside persistent substantial pyuria and leukocyte casts, which is not seen in =

Factors that warrant admission for intravenous (IV) nephritis, which can lead to chronic glomerular basement diuretics include lack of response after addition of a thiazide membrane changes but not acute glomerulonephritis. Fur- and/or potassium-sparing diuretic to a loop diuretic; acute thermore, neither acute viral encephalitis nor acyclovir is respiratory symptoms secondary to pulmonary edema; or associated with acute glomerulonephritis. significant ascites that raise concern for gut edema and Acute interstitial nephritis (AIN) (Option B) is a com- malabsorption of oral diuretics. These factors are not present mon cause of AKI and is characterized by inflammation and in this patient. A number of randomized clinical trials have edema of the interstitium. The classic clinical presentation of evaluated the efficacy of a continuous IV infusion of loop fever, rash, and peripheral eosinophilia occurs in only 10% to diuretics compared with IV bolus therapy (Options B, C). 30% of patients with AIN. Drug-induced AIN, especially due Findings indicated that continuous IV infusion is associated to antibiotics, is the most common cause of AIN and should with less ototoxicity than bolus injections of loop diuretics, be considered in any patient with AKI, a characteristic uri- but clear evidence of its diuretic superiority is lacking, at the nalysis, and history of any drug exposure. Drug-induced AIN minimum in heart failure patients. typically takes 7 to 10 days to develop and is characterized by w a This patient’s significant edema alongside persistent substantial pyuria and leukocyte casts, which is not seen in = nephrotic-range proteinuria and hypoalbuminemia does not this patient’s urinalysis results. = warrant discontinuation of prednisone (first-line therapy for Acute tubular necrosis (Option C) is usually suggested 7.) oC FSGS) for the addition of cyclosporine (second-line therapy by urine sediment that shows pigmented brown casts and sc = for FSGS) (Option D), as the patient has received glucocor- debris, which are not seen in this patient’s urinalysis results. cs ticoid therapy for only 3 weeks. In adults with FSGS, thera- wn Peas o peutic response can take up to 12 to 16 weeks. Therefore, it = would be premature to consider this patient refractory to e Intravenous acyclovir can cause acute kidney injury wn = glucocorticoid therapy. due to intratubular obstruction from acyclovir crystal <—

nephrotic-range proteinuria and hypoalbuminemia does not this patient’s urinalysis results. = warrant discontinuation of prednisone (first-line therapy for Acute tubular necrosis (Option C) is usually suggested 7.) oC FSGS) for the addition of cyclosporine (second-line therapy by urine sediment that shows pigmented brown casts and sc = for FSGS) (Option D), as the patient has received glucocor- debris, which are not seen in this patient’s urinalysis results. cs ticoid therapy for only 3 weeks. In adults with FSGS, thera- wn Peas o peutic response can take up to 12 to 16 weeks. Therefore, it = would be premature to consider this patient refractory to e Intravenous acyclovir can cause acute kidney injury wn = glucocorticoid therapy. due to intratubular obstruction from acyclovir crystal <— Hemodialysis with ultrafiltration (Option E) for edema precipitation. is reserved for patients with anasarca, significant kidney ¢ Correction of volume depletion is critical for the pre- dysfunction, and an inability to diurese on maximal doses vention and treatment of crystal-induced acute kidney of IV diuretics. injury.

Hemodialysis with ultrafiltration (Option E) for edema precipitation. is reserved for patients with anasarca, significant kidney ¢ Correction of volume depletion is critical for the pre- dysfunction, and an inability to diurese on maximal doses vention and treatment of crystal-induced acute kidney of IV diuretics. injury. Bibliography e In patients with the nephrotic syndrome and refrac- Mulay SR, Anders HJ. Crystal nephropathies: mechanisms of crystal- tory edema despite high-dose loop diuretics, adding a induced kidney injury. Nat Rev Nephrol. 2017;13:226-240. [PMID: thiazide diuretic and/or a potassium-sparing diuretic 28218266] doi:10.1038/nrneph.2017.10 is the appropriate next step in management. Item 106 Answer: B Bibliography Educational Objective: Treat hyperkalemia. Gupta S, Pepper RJ, Ashman N, et al. Nephrotic syndrome: oedema forma- tion and its treatment with diuretics. Front Physiol. 2018;9:1868. [PMID: 30697163] doi:10.3389/fphys.2018.01868 The most appropriate management is to add patiromer (Option B), a potassium binder, to treat this patient’s moder- ate hyperkalemia. Initial evaluation of hyperkalemia requires

Item 106 Answer: B Bibliography Educational Objective: Treat hyperkalemia. Gupta S, Pepper RJ, Ashman N, et al. Nephrotic syndrome: oedema forma- tion and its treatment with diuretics. Front Physiol. 2018;9:1868. [PMID: 30697163] doi:10.3389/fphys.2018.01868 The most appropriate management is to add patiromer (Option B), a potassium binder, to treat this patient’s moder- ate hyperkalemia. Initial evaluation of hyperkalemia requires Item 105 Answer: D a review of all medications, assessment of kidney function, and an ECG. Initial ECG manifestations include peaked pre- Educational Objective: Diagnose crystal-induced acute cordial T waves and a shortened QT interval. Hyperkalemia kidney injury in patients receiving intravenous acyclovir. frequently occurs in chronic kidney disease with an estimated The most likely cause of this patient’s acute kidney injury glomerular filtration rate <20 mL/min/1.73 m?. Hypoaldoste- (AKI) is intratubular obstruction (Option D). Intratubular ronism caused by inhibitors of the renin-angiotensin system, obstruction can cause AKI through precipitation of crystals heparin, type 4 (hyperkalemic distal) renal tubular acidosis, within the tubular lumen. Urinary findings include hema or primary adrenal insufficiency also cause hyperkalemia. turia, pyuria, and crystals. This patient received intravenous All potentially causative medications should be discontinued high-dose acyclovir, which can cause acute AKI due to intra- if possible. Although angiotensin receptor blockers (ARBs) tubular obstruction from acyclovir crystal precipitation. Pre- such as losartan frequently cause hyperkalemia by decreasing disposing factors for crystal-induced AKI include chronic aldosterone levels, guidelines recommend their use to slow kidney disease and volume depletion. Aggressive volume the progression of kidney disease and provide cardiovascular expansion is recommended during high-dose acyclovir ther- protection. This patient has severely increased albuminuria, apy for these patients. Correction of volume depletion is also which puts her at increased risk for both progressing to end- critical for the treatment of crystal-induced AKI as well as stage kidney disease and a cardiovascular event. Routine dis- discontinuation of the drug if possible. continuation of ARBs has been associated with worsening Acute glomerulonephritis (Option A) is not a likely outcomes; with the addition of effective potassium binders, cause of this patient’s AKI. This patient has hereditary discontinuation of ARBs is discouraged. Therefore, because

Item 105 Answer: D a review of all medications, assessment of kidney function, and an ECG. Initial ECG manifestations include peaked pre- Educational Objective: Diagnose crystal-induced acute cordial T waves and a shortened QT interval. Hyperkalemia kidney injury in patients receiving intravenous acyclovir. frequently occurs in chronic kidney disease with an estimated The most likely cause of this patient’s acute kidney injury glomerular filtration rate <20 mL/min/1.73 m?. Hypoaldoste- (AKI) is intratubular obstruction (Option D). Intratubular ronism caused by inhibitors of the renin-angiotensin system, obstruction can cause AKI through precipitation of crystals heparin, type 4 (hyperkalemic distal) renal tubular acidosis, within the tubular lumen. Urinary findings include hema or primary adrenal insufficiency also cause hyperkalemia. turia, pyuria, and crystals. This patient received intravenous All potentially causative medications should be discontinued high-dose acyclovir, which can cause acute AKI due to intra- if possible. Although angiotensin receptor blockers (ARBs) tubular obstruction from acyclovir crystal precipitation. Pre- such as losartan frequently cause hyperkalemia by decreasing disposing factors for crystal-induced AKI include chronic aldosterone levels, guidelines recommend their use to slow kidney disease and volume depletion. Aggressive volume the progression of kidney disease and provide cardiovascular expansion is recommended during high-dose acyclovir ther- protection. This patient has severely increased albuminuria, apy for these patients. Correction of volume depletion is also which puts her at increased risk for both progressing to end- critical for the treatment of crystal-induced AKI as well as stage kidney disease and a cardiovascular event. Routine dis- discontinuation of the drug if possible. continuation of ARBs has been associated with worsening Acute glomerulonephritis (Option A) is not a likely outcomes; with the addition of effective potassium binders, cause of this patient’s AKI. This patient has hereditary discontinuation of ARBs is discouraged. Therefore, because 173

Answers and Critiques of the beneficial cardiovascular and renal effects of blocking esophagus, kidneys, and cleft lip and palate. Mycophenolate angiotensin, if serum potassium is only mildly elevated (as mofetil is also contraindicated in women who are breastfeed- in this patient), the use of potassium binders may allow the ing because the drug is excreted into breast milk. This patient patient to continue use of losartan. Patiromer and sodium should discontinue this agent and, if continued immuno- zirconium cyclosilicate are two FDA-approved potassium suppression is required, be switched to azathioprine, which binders. The choice of binder is determined by patient and is generally safer and well tolerated in pregnancy. In diseases physician preference, as each agent has its advantages and such as systemic lupus erythematosus (SLE) in which myco- disadvantages. Sodium polystyrene sulfonate is no longer rec- phenolate mofetil is commonly used, patients should show ommended as a potassium binder due to its poor efficacy in stable disease for 3 to 6 months following discontinuation of lowering potassium and numerous reported adverse effects. the agent before proceeding with pregnancy. Adding a thiazide diuretic such as hydrochlorothiazide Hydroxychloroquine (Option A) has been used safely (Option A) may improve this patient’s hyperkalemia. How- in pregnancy. This patient who is planning a pregnancy

of the beneficial cardiovascular and renal effects of blocking esophagus, kidneys, and cleft lip and palate. Mycophenolate angiotensin, if serum potassium is only mildly elevated (as mofetil is also contraindicated in women who are breastfeed- in this patient), the use of potassium binders may allow the ing because the drug is excreted into breast milk. This patient patient to continue use of losartan. Patiromer and sodium should discontinue this agent and, if continued immuno- zirconium cyclosilicate are two FDA-approved potassium suppression is required, be switched to azathioprine, which binders. The choice of binder is determined by patient and is generally safer and well tolerated in pregnancy. In diseases physician preference, as each agent has its advantages and such as systemic lupus erythematosus (SLE) in which myco- disadvantages. Sodium polystyrene sulfonate is no longer rec- phenolate mofetil is commonly used, patients should show ommended as a potassium binder due to its poor efficacy in stable disease for 3 to 6 months following discontinuation of lowering potassium and numerous reported adverse effects. the agent before proceeding with pregnancy. Adding a thiazide diuretic such as hydrochlorothiazide Hydroxychloroquine (Option A) has been used safely (Option A) may improve this patient’s hyperkalemia. How- in pregnancy. This patient who is planning a pregnancy Pt ever, it could result in volume depletion with decreased would be recommended to continue taking this drug. = wn delivery of sodium to the potassium secretory sites, result- Hydroxychloroquine is initiated in every patient with SLE = ing in worsening hyperkalemia. In addition, this patient's who can tolerate it, because evidence suggests it reduces @ blood pressure is at goal and there is no indication to further disease-associated damage, prevents disease flares, and = nn y lower it. improves kidney and overall survival. In addition, hydroxy- 3 om When hyperkalemia is associated with changes on ECG, chloroquine may reduce the risk for thrombosis, liver dis- (=) =e intravenous calcium gluconate (Option C) should be admin- ease, and myocardial infarction; improve lipid profiles; and =. istered to stabilize the cardiac membrane by raising thresh- improve outcomes in high-risk pregnancies. aes Soe old potential. Because this patient’s serum potassium was Glucocorticoids such as prednisone (Option C) increase mo n only moderately elevated and her ECG was normal, calcium the risk for pregnancy-induced hypertension and diabetes gluconate is not indicated. mellitus but can be continued during pregnancy when the Providing this patient with no treatment is inappro- benefits outweigh the risks to the patient and fetus. Steps priate (Option D). Although her serum potassium is only can be taken to reduce the risk of glucocorticoid therapy moderately elevated, serum potassium levels >5 mEq/L during pregnancy, including using the lowest dose pos- (5 mmol/L) are associated with increased morbidity and sible for the shortest period of time; carefully managing mortality. preexisting medical conditions that may be exacerbated by glucocorticoid therapy (for example, osteoporosis, diabetes, and hypertension); and carefully monitoring for treatment e Potassium binders such as patiromer and sodium zir- adverse effects and providing early intervention should they conium cyclosilicate can be used to treat hyperkalemia arise. in patients with chronic kidney disease. Making no changes to this patient’s medication regimen

Pt ever, it could result in volume depletion with decreased would be recommended to continue taking this drug. = wn delivery of sodium to the potassium secretory sites, result- Hydroxychloroquine is initiated in every patient with SLE = ing in worsening hyperkalemia. In addition, this patient's who can tolerate it, because evidence suggests it reduces @ blood pressure is at goal and there is no indication to further disease-associated damage, prevents disease flares, and = nn y lower it. improves kidney and overall survival. In addition, hydroxy- 3 om When hyperkalemia is associated with changes on ECG, chloroquine may reduce the risk for thrombosis, liver dis- (=) =e intravenous calcium gluconate (Option C) should be admin- ease, and myocardial infarction; improve lipid profiles; and =. istered to stabilize the cardiac membrane by raising thresh- improve outcomes in high-risk pregnancies. aes Soe old potential. Because this patient’s serum potassium was Glucocorticoids such as prednisone (Option C) increase mo n only moderately elevated and her ECG was normal, calcium the risk for pregnancy-induced hypertension and diabetes gluconate is not indicated. mellitus but can be continued during pregnancy when the Providing this patient with no treatment is inappro- benefits outweigh the risks to the patient and fetus. Steps priate (Option D). Although her serum potassium is only can be taken to reduce the risk of glucocorticoid therapy moderately elevated, serum potassium levels >5 mEq/L during pregnancy, including using the lowest dose pos- (5 mmol/L) are associated with increased morbidity and sible for the shortest period of time; carefully managing mortality. preexisting medical conditions that may be exacerbated by glucocorticoid therapy (for example, osteoporosis, diabetes, and hypertension); and carefully monitoring for treatment e Potassium binders such as patiromer and sodium zir- adverse effects and providing early intervention should they conium cyclosilicate can be used to treat hyperkalemia arise. in patients with chronic kidney disease. Making no changes to this patient’s medication regimen e Use of potassium binders in patients with chronic kid- (Option D) would not be appropriate because mycophe- ney disease may allow continuation of essential medi- nolate mofetil is teratogenic and is contraindicated during pregnancy. cations, such as inhibitors of the renin-angiotensin system.

e Use of potassium binders in patients with chronic kid- (Option D) would not be appropriate because mycophe- ney disease may allow continuation of essential medi- nolate mofetil is teratogenic and is contraindicated during pregnancy. cations, such as inhibitors of the renin-angiotensin system. e¢ Mycophenolate mofetil is teratogenic and is contrain- Bibliography dicated in pregnancy. Evans M, Palaka E, Furuland H, et al. The value of maintaining normokalae- mia and enabling RAASi therapy in chronic kidney disease. BMC e In diseases in which mycophenolate mofetil is used, Nephrol. 2019;20:31. [PMID: 30704421] doi:10.1186/s12882-019-1228-y patients should show stable disease for 3 to 6 months following discontinuation of the agent before pro- Item 107 Answer: B ceeding with pregnancy.

e¢ Mycophenolate mofetil is teratogenic and is contrain- Bibliography dicated in pregnancy. Evans M, Palaka E, Furuland H, et al. The value of maintaining normokalae- mia and enabling RAASi therapy in chronic kidney disease. BMC e In diseases in which mycophenolate mofetil is used, Nephrol. 2019;20:31. [PMID: 30704421] doi:10.1186/s12882-019-1228-y patients should show stable disease for 3 to 6 months following discontinuation of the agent before pro- Item 107 Answer: B ceeding with pregnancy. Educational Objective: Discontinue mycophenolate Bibliography mofetil in a patient who is planning pregnancy. ACOG Committee opinion no. 776: immune modulating therapies in preg- Mycophenolate mofetil (Option B) should be discontinued nancy and lactation. Obstet Gynecol. 2019;133:e287-e295. [PMID: 30913201] doi:10.1097/AOG.0000000000003176 in this patient before conception. Before discontinuation of mycophenolate and attempted conception, steps should be taken to ensure disease stability in this patient. Pregnancy Item 108 Answer: A planning is essential for ensuring positive outcomes and Educational Objective: Treat a patient with diabetic includes adjusting medications and optimizing clinical status. kidney disease using a sodium-glucose cotransporter This patient is taking mycophenolate mofetil, a teratogenic 2 inhibitor. agent that is contraindicated in pregnancy. Documented risks with mycophenolate mofetil use include first-trimester preg- The most appropriate treatment is to add canagliflozin nancy loss and fetal malformations of the distal limbs, heart, (Option A). There are a limited number of interventions

Educational Objective: Discontinue mycophenolate Bibliography mofetil in a patient who is planning pregnancy. ACOG Committee opinion no. 776: immune modulating therapies in preg- Mycophenolate mofetil (Option B) should be discontinued nancy and lactation. Obstet Gynecol. 2019;133:e287-e295. [PMID: 30913201] doi:10.1097/AOG.0000000000003176 in this patient before conception. Before discontinuation of mycophenolate and attempted conception, steps should be taken to ensure disease stability in this patient. Pregnancy Item 108 Answer: A planning is essential for ensuring positive outcomes and Educational Objective: Treat a patient with diabetic includes adjusting medications and optimizing clinical status. kidney disease using a sodium-glucose cotransporter This patient is taking mycophenolate mofetil, a teratogenic 2 inhibitor. agent that is contraindicated in pregnancy. Documented risks with mycophenolate mofetil use include first-trimester preg- The most appropriate treatment is to add canagliflozin nancy loss and fetal malformations of the distal limbs, heart, (Option A). There are a limited number of interventions 174

___ Answers and Critiques proven to slow the decline of kidney function in patients with Adding losartan (Option C), an angiotensin receptor chronic kidney disease (CKD). Proven interventions include blocker (ARB), is contraindicated for this patient, as she is glycemic control, blood pressure control, renin-angiotensin currently receiving lisinopril, an ACE inhibitor. Blockade of system (RAS) blockers, and avoidance of renal toxins. For the RAS has been shown to slow the rate of progression for patients with diabetic kidney disease, the use of sodium- proteinuric CKD and is indicated for all patients who can glucose cotransporter 2 (SGLT2) inhibitors slows the progres- tolerate this medication class. However, dual blockade with sion of CKD and reduces the risk for death from kidney or an ACE inhibitor and an ARB results in more adverse events cardiovascular complications. For this patient with stage G3 without additional kidney benefit. CKD with nephrotic-range proteinuria due to type 2 diabetes mellitus, the SGLT2 inhibitor canagliflozin should be added to her medication regimen. Glucagon-like peptide-1 (GLP-1) e Sodium-glucose cotransporter 2 inhibitors slow the receptor agonists such as liraglutide are also suggested by the progression of chronic kidney disease and reduce the American Diabetes Association because they reduce the risks risk for death from kidney or cardiovascular compli- n ov for cardiovascular events and hypoglycemia and appear to cations in patients with diabetic kidney disease. =]

American Diabetes Association because they reduce the risks risk for death from kidney or cardiovascular compli- n ov for cardiovascular events and hypoglycemia and appear to cations in patients with diabetic kidney disease. =] possibly slow CKD progression. i e Glucagon-like peptide-1 receptor agonists reduce the Glyburide (Option B) is a second-generation sulfonyl- = risks for cardiovascular events and hypoglycemia and s) urea; pioglitazone (Option D) is a thiazolidinedione; and <3 appear to possibly slow chronic kidney disease pro- e sitagliptin (Option E) is a dipeptidyl peptidase 4 inhibitor. co gression. Drugs from these classes have a neutral effect on the pro- wn 7 o gression of CKD. The use of glyburide in patients with CKD Bibliography = ” is generally avoided because of the risk for hypoglycemia. = Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin Thiazolidinediones are used with caution in patients with = and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. CKD due to the potential for fluid retention. 2019;380:2295-2306. [PMID: 30990260] doi:10.1056/NEJMoa1811744

possibly slow CKD progression. i e Glucagon-like peptide-1 receptor agonists reduce the Glyburide (Option B) is a second-generation sulfonyl- = risks for cardiovascular events and hypoglycemia and s) urea; pioglitazone (Option D) is a thiazolidinedione; and <3 appear to possibly slow chronic kidney disease pro- e sitagliptin (Option E) is a dipeptidyl peptidase 4 inhibitor. co gression. Drugs from these classes have a neutral effect on the pro- wn 7 o gression of CKD. The use of glyburide in patients with CKD Bibliography = ” is generally avoided because of the risk for hypoglycemia. = Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin Thiazolidinediones are used with caution in patients with = and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. CKD due to the potential for fluid retention. 2019;380:2295-2306. [PMID: 30990260] doi:10.1056/NEJMoa1811744 175

Note: Page numbers followed by f and t denote figure and table, respectively. quantification of, 3 Test questions are indicated by Q. screening for, 8-9, 47, Q91 Albuterol, 17, Q1 A Alcohol, hypertension and, 33t Abacavir, TIN and, 42t Alcohol ingestion, hypomagnesemia and, 19 Abdominal compartment syndrome (ACS), 68-69, Q59 Alcoholic ketoacidosis, 4, 22, Q92 Acanthocytes, 5, 7f Aldosterone, 24-25, 31t, 38 ACE inhibitors Aldosterone receptor antagonists, 33-34 adverse effects of, 24, 34, 82 Aliskiren, for hypertension, 34 for Black patients, 40-41 Alkali therapy, for metabolic acidosis, 82 contraindications, 73 Alkylating agents, for minimal change glomerulopathy, 49 DKD management and, 47 Allopurinol, for uric acid crystal prevention, 68, 72 for hypertension, 33, 34t, 40 o-Blockers, for hypertension, 33, 34t for IgA nephropathy, Q27 Alport syndrome. See Hereditary nephritis precautions in pregnancy, 40 Aluminum hydroxide, for CKD-bone and mineral disorder, 81t prerenal AKI and, 63 Ambulatory blood pressure monitoring (ABPM), 28, Q14 TIN and, 42t Amiloride, 17, 34, Q40 Acetaminophen, 42t, 43-44 Aminoglycosides, 19, 64 Acetazolamide, 23, 26 5-Aminosalicylates, TIN and, 42t Acetoacetate, detection of, 4 Amlodipine, 34, Q22, Q50, Q52, Q68 Acetohydroxamic acid, 72 Amlodipine-valsartan, for hypertension, Q32 Acetone, detection of, 4 Ammonia (NH,), tubular production of, 23 Acid-base disorders, 19-26, 19f, 20f, 20t Amoxicillin, TIN and, 42t Acquired cystic kidney disease, 88, Q5 Amphotericin B, 24, 64 Acute coronary syndrome (ACS), IV drugs for, 40t Amyloidosis, 57, Q99 Acute glomerulonephritis, 46, 63t, 65 Anabolic steroids, 30t, 42t, Q98 Acute interstitial nephritis (AIN), 5, 63t, 65, Q19 Analgesic nephropathy, 42t, 43-44 Acute kidney injury (AKI) Analgesics, 42t, 43-44 ATN versus, 62 ANCA-associated glomerulonephritis, 51 crystal-induced, Q105 Anemia, 43t, 81t definition of, 60, 60t Angioedema, description of, 34 diagnosis of, 62-63, 62t, 63t Angioplasty, in fibromuscular dysplasia, 38 epidemiology of, 60-62 Angiotensin receptor blockers (ARBs) hypertension and, 27, 36-37 contraindications, 73 intratubular obstruction and, Q105 DKD management and, 47 intrinsic, 63-65 for hypertension, 33, 34t, 37, 40 IV drugs for, 40t for IgA nephropathy, Q27 management of, 69-70 nephrotoxicity of, 82 microscopy in, 63t precautions in pregnancy, 40 minimal change glomerulopathy and, Q100 prerenal AKI and, 63 nonpharmacologic causes of, 61t for proteinuria, 82 pathophysiology of, 60-62 renal tubular acidosis and, 24 pharmacologic causes of, 61t TIN and, 42t posttransplant, 87 Anion gap, 20, 24 prerenal, 63 Anion gap hyperchloremic metabolic acidosis, 81 rasburicase in, Q70 Anion gap metabolic acidosis, 21-24, 23t recovery from, 76 Antacids, hypermagnesemia and, 19 renal replacement therapy for, Q16 Antibiotics, 42t, 65 Acute phosphate nephropathy, AKI and, 67 Anticoagulation, hematuria and, 9-10 Acute pulmonary edema, nitroglycerine for, 40t Antideoxyribonuclease B levels, 54 Acute tubular necrosis (ATN), 5, 62-65, 64t, 67, Antidepressants, 12, 30t Q43, Q51 Antidiuretic hormone (ADH), 11, 13 Acute vascular syndromes, 63t Antiepileptic drugs, TIN and, 42t Acute-onset severe hypertension, 73 Anti-glomerular basement membrane antibody disease, 50-51, Q63 Acyclovir, 5, 67, Q105 Antihyaluronidase, as marker of IRGN, 54 Addison disease, renal tubular acidosis and, 24 Antihypertensive drugs, 39t, 42t Adynamic bone disease, 79 Antineoplastic agents, 42t, 44 Age/aging Antineutrophil cytoplasmic antibodies (ANCA), 50-51 CKD and, 84 Antinuclear antibody (ANA), SLE and, Q45 hypertension and, 41, Q74 Anti-phospholipase A2 receptor antibodies, Q75 AIN. See Acute interstitial nephritis (AIN) Antiplatelet medications, hematuria and, 9-10 AKI. See Acute kidney injury (AK1) Antiretroviral drugs, TIN and, 42t Albumin, 8-9, 20, Q25 Antistreptokinase, as marker of IRGN, 54 Albumin-creatinine ratio, 37, Q29, Q91 Antistreptolysin O, as marker of IRGN, 54 Albuminuria Anxiety, 26, 89 CKD staging and, 75 Aortic coarctation, 31t definition of, 8t Aortic dissection, esmolol use in, 40t, Q30 hypertension and, 36 Apolipoprotein L1 nephropathy, 60 lisinopril for hypertension in, Q39 Appetite suppressants, blood pressure and, 30t losartan for hypertension in, Q37 ARBs. See Angiotensin receptor blockers (ARBs) nephrotic syndrome and, 46 Aristolochia clematitis, 44

Note: Page numbers followed by f and t denote figure and table, respectively. quantification of, 3 Test questions are indicated by Q. screening for, 8-9, 47, Q91 Albuterol, 17, Q1 A Alcohol, hypertension and, 33t Abacavir, TIN and, 42t Alcohol ingestion, hypomagnesemia and, 19 Abdominal compartment syndrome (ACS), 68-69, Q59 Alcoholic ketoacidosis, 4, 22, Q92 Acanthocytes, 5, 7f Aldosterone, 24-25, 31t, 38 ACE inhibitors Aldosterone receptor antagonists, 33-34 adverse effects of, 24, 34, 82 Aliskiren, for hypertension, 34 for Black patients, 40-41 Alkali therapy, for metabolic acidosis, 82 contraindications, 73 Alkylating agents, for minimal change glomerulopathy, 49 DKD management and, 47 Allopurinol, for uric acid crystal prevention, 68, 72 for hypertension, 33, 34t, 40 o-Blockers, for hypertension, 33, 34t for IgA nephropathy, Q27 Alport syndrome. See Hereditary nephritis precautions in pregnancy, 40 Aluminum hydroxide, for CKD-bone and mineral disorder, 81t prerenal AKI and, 63 Ambulatory blood pressure monitoring (ABPM), 28, Q14 TIN and, 42t Amiloride, 17, 34, Q40 Acetaminophen, 42t, 43-44 Aminoglycosides, 19, 64 Acetazolamide, 23, 26 5-Aminosalicylates, TIN and, 42t Acetoacetate, detection of, 4 Amlodipine, 34, Q22, Q50, Q52, Q68 Acetohydroxamic acid, 72 Amlodipine-valsartan, for hypertension, Q32 Acetone, detection of, 4 Ammonia (NH,), tubular production of, 23 Acid-base disorders, 19-26, 19f, 20f, 20t Amoxicillin, TIN and, 42t Acquired cystic kidney disease, 88, Q5 Amphotericin B, 24, 64 Acute coronary syndrome (ACS), IV drugs for, 40t Amyloidosis, 57, Q99 Acute glomerulonephritis, 46, 63t, 65 Anabolic steroids, 30t, 42t, Q98 Acute interstitial nephritis (AIN), 5, 63t, 65, Q19 Analgesic nephropathy, 42t, 43-44 Acute kidney injury (AKI) Analgesics, 42t, 43-44 ATN versus, 62 ANCA-associated glomerulonephritis, 51 crystal-induced, Q105 Anemia, 43t, 81t definition of, 60, 60t Angioedema, description of, 34 diagnosis of, 62-63, 62t, 63t Angioplasty, in fibromuscular dysplasia, 38 epidemiology of, 60-62 Angiotensin receptor blockers (ARBs) hypertension and, 27, 36-37 contraindications, 73 intratubular obstruction and, Q105 DKD management and, 47 intrinsic, 63-65 for hypertension, 33, 34t, 37, 40 IV drugs for, 40t for IgA nephropathy, Q27 management of, 69-70 nephrotoxicity of, 82 microscopy in, 63t precautions in pregnancy, 40 minimal change glomerulopathy and, Q100 prerenal AKI and, 63 nonpharmacologic causes of, 61t for proteinuria, 82 pathophysiology of, 60-62 renal tubular acidosis and, 24 pharmacologic causes of, 61t TIN and, 42t posttransplant, 87 Anion gap, 20, 24 prerenal, 63 Anion gap hyperchloremic metabolic acidosis, 81 rasburicase in, Q70 Anion gap metabolic acidosis, 21-24, 23t recovery from, 76 Antacids, hypermagnesemia and, 19 renal replacement therapy for, Q16 Antibiotics, 42t, 65 Acute phosphate nephropathy, AKI and, 67 Anticoagulation, hematuria and, 9-10 Acute pulmonary edema, nitroglycerine for, 40t Antideoxyribonuclease B levels, 54 Acute tubular necrosis (ATN), 5, 62-65, 64t, 67, Antidepressants, 12, 30t Q43, Q51 Antidiuretic hormone (ADH), 11, 13 Acute vascular syndromes, 63t Antiepileptic drugs, TIN and, 42t Acute-onset severe hypertension, 73 Anti-glomerular basement membrane antibody disease, 50-51, Q63 Acyclovir, 5, 67, Q105 Antihyaluronidase, as marker of IRGN, 54 Addison disease, renal tubular acidosis and, 24 Antihypertensive drugs, 39t, 42t Adynamic bone disease, 79 Antineoplastic agents, 42t, 44 Age/aging Antineutrophil cytoplasmic antibodies (ANCA), 50-51 CKD and, 84 Antinuclear antibody (ANA), SLE and, Q45 hypertension and, 41, Q74 Anti-phospholipase A2 receptor antibodies, Q75 AIN. See Acute interstitial nephritis (AIN) Antiplatelet medications, hematuria and, 9-10 AKI. See Acute kidney injury (AK1) Antiretroviral drugs, TIN and, 42t Albumin, 8-9, 20, Q25 Antistreptokinase, as marker of IRGN, 54 Albumin-creatinine ratio, 37, Q29, Q91 Antistreptolysin O, as marker of IRGN, 54 Albuminuria Anxiety, 26, 89 CKD staging and, 75 Aortic coarctation, 31t definition of, 8t Aortic dissection, esmolol use in, 40t, Q30 hypertension and, 36 Apolipoprotein L1 nephropathy, 60 lisinopril for hypertension in, Q39 Appetite suppressants, blood pressure and, 30t losartan for hypertension in, Q37 ARBs. See Angiotensin receptor blockers (ARBs) nephrotic syndrome and, 46 Aristolochia clematitis, 44 177