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Nephrology Kidney Biopsy Kidney biopsy should be considered in patients with: . glomerular hematuria o severely increased albuminuria . acute or chronic disease ofunclear origin o kidney transplant dysfunction Common contraindications to kidney biopsy include bleeding diatheses, severe anemia, UTI, hydronephrosis, uncontrolled hypertension, renal tumor, and atrophic kidneys. Hyponatremia Diagnosis The first step in assessing low serum sodium is to determine whether true hyponatremia is present by measuring serum osmolality. Isotonic hlponatremia is a laboratory artifact caused by severe hyperlipidemia or hyperproteinemia. In isotonic hyponatremia, the measured osmolality is normal. If true hyponatremia exists, classi$r it as hypertonic or hypotonic. Hypertonic hyponatremia (osmolality >295 mOsm/kg HrO) is caused by the presence of an osmotically active substance, such as: o glucose (most common) . BUN . alcohols o mannitol . sorbitol . glycine (bladder irrigation during urologic procedures) Hypotonic hyponatremia (osmolality <275 mOsm/kg HrO) is the most common form of hyponatremia and is further classified based on the patient's volume status.

Hypertonic hyponatremia (osmolality >295 mOsm/kg HrO) is caused by the presence of an osmotically active substance, such as: o glucose (most common) . BUN . alcohols o mannitol . sorbitol . glycine (bladder irrigation during urologic procedures) Hypotonic hyponatremia (osmolality <275 mOsm/kg HrO) is the most common form of hyponatremia and is further classified based on the patient's volume status. STUDY IABLE: Evaluating Hypotonic Hyponatremia Volume Status Laboratory Studies Differential Diagnosis Hypovo lemic (hypotension, Spot urine sodium <20 mEq/L Gl or kidney sodium losses, tachyca rdia) mineralocorticoid insufficiency BUN/creatinine >20:1 Hypervolemic (edema, ascites) Spot urine sodium <20 mEq/L(HF and cirrhosis in absence of HF, cirrhosis, kidney failure diuretic therapy) Spot urine sodium >20 mEq/L (acute and chronic kidney failure) lsovolemic (normal volume) Spot urine sodium >20 mEq/L SIADH, hypothyroidism, adrenal insufficiency Urine osmolality usually >1 00 mOsm/kg H2O lsovolemic (normal volume) Spot urine sodium <20 mEq/L Compulsive water drinking Urine osmolality 50 to 100 mOsm/kg H2O 262

Nephrology Causes of SIADH include malignancy (SCLC); intracranial pathologr; and pulmonary diseases, especially those that increase intrathoracic pressure and decrease venous return to the heart. Many medications can cause SIADH, including thiazides, SSRIs, tricyclic antidepressants, opioids, phenothiazines, and carbamazepine. DOT'T BE TRICKED o Do not miss adrenal insulEciency as a cause of hypotonic hyponatremia. Treatment IV volume replacement with normal saline is indicated for hypovolemic hypotonic hyponatremia resulting from volume depletion. Acute symptomatic isovolemic hypotonic hyponatremia (urine osmolality >100 mOsm/kg HrO) should be treated with a 100 mL bolus of 3% saline to increase the serum sodium by 2.0 to 3.0 mEq/L. Chronic symptomatic isovolemic hlpotonic hyponatremia (>48 hours or unknown) should be treated to a target of 4 to 6 mEq/L in 24 hours. If neurologic impairment is significant (seizures or coma), sodium can be acutely increased 2.0-4.0 mEq/L using a bolus of 3% saline as long as the total increase remains <10 mEq/L in 24 hours. If the serum sodium concentration is overcorrected, administer desmopressin and IV 5% dextrose in water. Central pontine myelinolysis (osmotic demyelination syndrome) may occur if hyponatremia is corrected too rapidly. Water restriction is used initially for asymptomatic or minimally symptomatic outpatients with SIADH. Demeclocycline can also be used for outpatients who do not respond to fluid restriction. The IV V, and V, receptor antagonist conivaptan and the oral V, receptor antagonist tolvaptan (vaptans) are approved for treatment of euvolemic and hypervolemic hyponatremia. Oral tolvap- tan should be reserved for the management of a serum sodium concentration <120 mEq/L and persistent SIADH that has failed water restriction. No data show that the vaptans are associated with improved patient outcomes compared with conventional therapy. DOil'T BE TRICKED . Vaptan agents should not be used to treat hypovolemic hyponatremia or acute symptomatic hlponatremia. . Unless documentation indicates that hyponatremia is acute, treat all cases of hyponatremia as chronic.

Water restriction is used initially for asymptomatic or minimally symptomatic outpatients with SIADH. Demeclocycline can also be used for outpatients who do not respond to fluid restriction. The IV V, and V, receptor antagonist conivaptan and the oral V, receptor antagonist tolvaptan (vaptans) are approved for treatment of euvolemic and hypervolemic hyponatremia. Oral tolvap- tan should be reserved for the management of a serum sodium concentration <120 mEq/L and persistent SIADH that has failed water restriction. No data show that the vaptans are associated with improved patient outcomes compared with conventional therapy. DOil'T BE TRICKED . Vaptan agents should not be used to treat hypovolemic hyponatremia or acute symptomatic hlponatremia. . Unless documentation indicates that hyponatremia is acute, treat all cases of hyponatremia as chronic. TESTYOURSETF A S3-year-old man has a 3-week history of increasing weakness and anorexia. On physical examination, his volume status is normal. Laboratory studies: serum creatinine, 0.8 mg/dl; serum sodium, 123 mEq/L; potassium, 3.4 mEq/L; and urine sodium, 110 mEq/L. ANSWER: For diagnosis, choose SIADH. For management, select semm osmolality measurement to confirm the presence of hlpo-osmolality. If hypo-osmolality is present, the patient likely has SIADH (most common), thyroid disease, or adrenal insuffi- ciency. Hypernatremia Diagnosis Hypernatremia is defined as a serum sodium level >145 mEq/L. Severe hypernatremia indicates a defective thirst mechanism, inadequate access to water (older patients in nursing homes), a kidney concentrating defect (DI, most commonly caused by lithium), and/or impaired pituitary secretion of ADH (e.g., sarcoidosis). Most commonly, hypematremia results from loss of hypotonic fluids (GI, kidney, skin) with inadequate water replacement. 263

Nephrology Treatment Administer oral slow-release magnesium (mild to moderate hypomagnesemia) or IV magnesium sulfate to achieve a serum magnesium level >1 mg/dl. TESTYOURSELF A 3O-year-old woman with Crohn disease has an ileostomy. For the past week, she has noted increased ostomy output, weakness, and paresthesias. Laboratory studies show serum sodium, 129 mEqlL; potassium, 2.9 mEqlL; bicarbonate, 18 mEq/L; calcium, 5.5 mg/dl; and phosphorus, 1.3 mg/dl. After treatment with isotonic saline plus potassium chloride and sodium bicarbonate, the bicarbonate concentration is 22 mEq/L. However, the serum potassium level is still 2.9 mEq/L, and the serum calcium level is s.3 mg/dl. ANSWER: For diagnosis, choose hypomagnesemia. For management, measure magnesium level and, if low, begin IV magnesium replacement. Hypophosphatemia Diagnosis Phosphate is primarily excreted through the kidneys and is reabsorbed mainly in the proximal tubule. The primary hormonal factors regulating phosphorus balance are PTH (which decreases phosphorus reabsorption and promotes kidney phosphate excretion) and calcitriol (which stimulates phosphate absorption in the gut). Characteristic findings in severe hypophos- phatemia are HE muscle weakness, rhabdomyolysis, hemolytic anemia, and metabolic encephalopathy. Common causes include: . refeeding after starvation . insulin administration for severe hyperglycemia . hungry bone syndrome following parathyroidectomy . respiratory alkalosis o chronic diarrhea o chronic alcoholism o hyperparathyroidism r vitamin D deficiency If the cause of hypophosphatemia is not evident from the history a 24-hour urine phosphate collection or calculation of the FEeoo from a random urine sample can help differentiate renal from extrarenal causes. The FEeoo can be calculated as follows: (Urine POo x Serum Creatinine x 100)/(Serum POo x Urine Creatinine) Urine phosphate excretion >100 mg/d or an FEeoo >57o indicates renal phosphate wasting. Treatment In asymptomatic patients, administer oral phosphorus replacement as a sodium or potassium salt. parenteral therapy with either of these agents is indicated for symptomatic patients or for those whose phosphorus level is <2 mg/dl. 266

Nephrology Normal Anion Gap Acidosis Common causes of normal anion gap metabolic acidosis include: o GI HCO: loss (diarrhea) o kidney HCo., Ioss (type 2 proximal RTA) . reduced kidney H* secretion (type t hypokalemic distal RTA, type 4 hyperkalemic distal RTA) . Fanconi syndrome (phosphaturia, glucosuria, uricosuria, aminoaciduria) o carbonic anhydrase inhibitor use (acetazolamide and topiramate) Urine Anion Gap Increased acid excretion by the kidney is reflected as a marked increase in urine ammonium. Because chloride is excreted into the urine in amounts equal to ammonium, the amount of chloride in the urine reflects the amount of ammonium present. The ability to excrete acid in the form of ammonia is calculated with the UAG. The UAG is defined as (urine [Na*] + urine [K'J) - urine [Cl l. . During normal anion gap metabolic acidosis resulting from extrarenal bicarbonate loss (diarrhea), the kidney will excrete increased urine ammonium (and chloride), resulting in a negative UAG. o During impaired urine acidification caused by type t hlpokalemic distal RTA, urine ammonium (and chloride) excretion is impaired, with the UAG being positive. Renal Tubular Acidosis Normal anion gap metabolic acidosis is seen in all three types of RTA.

. During normal anion gap metabolic acidosis resulting from extrarenal bicarbonate loss (diarrhea), the kidney will excrete increased urine ammonium (and chloride), resulting in a negative UAG. o During impaired urine acidification caused by type t hlpokalemic distal RTA, urine ammonium (and chloride) excretion is impaired, with the UAG being positive. Renal Tubular Acidosis Normal anion gap metabolic acidosis is seen in all three types of RTA. *TUDY T&ELEr Differential Diagnosis of RenalTubular Acidosis Diagnosis Metabolic Findings Associated Findings Type t hypokalemic distal RTA Normal anion gap metabolic acidosis, Nephrolithiasis and nephrocalcinosis, hypokalemia, positive UAG, urine pH >5.5 autoimmune disorders (SLE, Sjogren (only in the setting of systemic acidosis), serum syndrome), amphotericin B use, urinary lHCO3l= 10 mEq/L obstruction Type 2 proximal RTA Normal anion gap metabolic acidosis, normal Glycosuria, phosphaturia, hypouricemia, or negative UAG, hypokalemia, urine pH <5.5, aminoaciduria (Fanconi syndrome); serum IHCO3] = 16-18 mEqi L tubular proteinuria Type 4 hyperkalemic distal RTA Normal anion gap metabolic acidosis, Diabetes mellitus, urinary tract obstruction (hyporeninemic hypoaldosteronism) hyperkalemia, positive UAG, urine pH <5.5 Treatment In distal (type t) RTA, administration of bicarbonate usually corrects the metabolic acidosis. The potassium deficit should be corrected before correcting the acidemia. In proximal 11ype 2) RIA, correction of acidemia with bicarbonate therapy is often not possible. The addition of a thiazide diu- retic may help by inducing volume depletion, lowering the GFR, and thereby decreasing the flltered load of bicarbonate. The addition of a potassium-sparing diuretic may limit the degree of kidney potassium wasting.

In proximal 11ype 2) RIA, correction of acidemia with bicarbonate therapy is often not possible. The addition of a thiazide diu- retic may help by inducing volume depletion, lowering the GFR, and thereby decreasing the flltered load of bicarbonate. The addition of a potassium-sparing diuretic may limit the degree of kidney potassium wasting. In type 4 RIA, the primary goal of therapy is to correct the hyperkalemia, which will treat the acid-base disturbance. These patients, often with early CKD and diabetes, may develop severe hyperkalemia following treatment with ACE inhibitors or ARBs. 268

Nephrology TESTYOURSELF A 31-year old woman with IBD passes a kidney stone. Serum sodium is l42mEqlL, potassium is 2.9 mEqlL, chloride is 112 mEq/L, and bicarbonate is 20 mEq/L. Urine pH is 6.5. ANSWER: For diagnosis, choose type I hlpokalemic distal RIA. Delta-Delta In increased anion gap acidosis, the expected ratio between the change in anion gap (measured anion gap normal anion gap) and the change in plasma [HCO3] (normal HCO., measured HCOr) concentration (A anion gap/A [HCO,]I) is 1 to 2. o lf (A anion gap/A [HCO"I) is <0.5-1, consider concurrent normal anion gap acidosis. . If (A anion gap/A [HCO3I) is >2, consider concurrent metabolic a]kalosis. Metabolic alkalosis is often caused by upper GI loss of hydrogen chloride from vomiting or by kidney loss of hydrogen chloride during diuretic therapy. Metabolic alkalosis is maintained by extracellular fluid volume contraction, chloride depletion, hypoka- Iemia, or elevated aldosterone activity. You must be able to answer questions like these: o Problem 1: pH,7.31; arterial Pcor, 10 mm Hg; sodium, 127 mBqlL; chloride, 99 mBqlL; bicarbonate, 5 mEq/L. Answer: Mixed increased anion gap and normal anion gap metabolic acidosis and respiratory alkalosis (triple acid-base disorder) r Problem 2:pH,7.2O; arterial Pcor, 23 mm Hg; sodium, 734mBqlL; chloride, B0 mEq/L; bicarbonate, 8 mEq/L. Answer: Mixed increased anion gap metabolic acidosis and metabolic alkalosis (double acid-base disorder) Alcohol Poisoning Diagnosis Determine the presence of an osmolal gap, which is the difference between measured and calculated osmolality. The calculated plasma osmolaliSz = (2 x serum [Na*]) + [BUN]/2.8 + blood [g]ucosel/18; sodium concentration is measured as mEq/L, and BUN and glucose concentration are measured as mg/dl. The normal osmolal gap is 10 mOsm/kg HrO. If a larger gap exists, consider alcohol poisoning as the source of unmeasured osmoles. Ethanol is the most common cause of alcohol poisoning. Methanol, isopropyl alcohol, and ethylene glycol may also increase the osmolal gap.

Alcohol Poisoning Diagnosis Determine the presence of an osmolal gap, which is the difference between measured and calculated osmolality. The calculated plasma osmolaliSz = (2 x serum [Na*]) + [BUN]/2.8 + blood [g]ucosel/18; sodium concentration is measured as mEq/L, and BUN and glucose concentration are measured as mg/dl. The normal osmolal gap is 10 mOsm/kg HrO. If a larger gap exists, consider alcohol poisoning as the source of unmeasured osmoles. Ethanol is the most common cause of alcohol poisoning. Methanol, isopropyl alcohol, and ethylene glycol may also increase the osmolal gap. STUDY TABLE: Presentation and Treatment of Alcohol Poisoning Alcohol Common Sources Major Findings Anion Gap Osmolar Gap Treatment Ethanol Alcoholic beverages CNS depression No Yes Supportive care (0.9% saline lV, glucose, thiamine) Flank pain, hematuria, oliguria lsopropyl Rubbing alcohol CNS depression No Yes Supportive care (similar to alcohol ethanol) 1 Ketones Methanol Windshield wiperfluid CNS depression Yes Yes Fomepizole De-icing solutions Vision loss Dialysis (if severe) Folic acid Ethylene Antifreeze CNS depression Yes Yes Fomepizole glycol De-icing solutions Acute kidney injury Dialysis (if severe) Calcium oxalate crystals in the u rine 269

Nephrology & + + $ fl- =ry = Cakium Oxalate Crystals: Characteristic envelope'shaped calcium oxalate dihy- drate crystals, which may be seen in late ethylene glycol intoxication. Hypertension Diagnosis Before labeling a person as having hypertension, use an average BP based on two or more readings obtained on two or more occasions. Out-of-office ABPM and HBPM are recommended to conflrm the diagnosis of hypertension and for titration of BP-lowering medication. White coat hypertension. In adults with an untreated SBP >130 but <160 mm Hg or DBP >80 but <100 mm Hg, it is reason able to evaluate for the presence of white coat hypertension using either daytime ABPM or HBPM before diagnosis of hyper tension. Masked hypertension. Masked hypertension is defined as elevated BP detected by ABPM or HBPM but with a normal office BP measurement. In adults with elevated office BP (120 7291<80 mm Hg) but not meeting the criteria for hypertension, evaluating for masked hypertension with daytime ABPM or HBPM is reasonable. Target BP for older adult patients. The ACC/AHA target SBP for noninstitutionalized, ambulatory community-dwelling patients aged 265 years is <130 mm Hg. The ACP guideline recommends a target SBP <150 mm Hg in patients aged >60 years. Target BP for patients with selected comorbidities. The ACC/AHA recommends a target BP <130/80 mm Hg for all patients with comorbidities, including all forms of ASCVD, HF, CKD, and diabetes. The ADA recommends a target BP <140/80 mm Hg for patients with diabetes; a target BP <130/80 mm Hg may be considered if 10 year ASCVD risk is >15'7,. ACP guidelines indicate a target SBP <140 rhm Hg may be reasonable in some patients aged 260 years at high cardiovascular risk or with a history of stroke or TIA based on individualized assessment. Secondary hypertension. Most patients with established hypertension have primary hypertension. Consider secondary hyper- tension in patients who have atypical clinical features (ear$ onset, absent family history hypokalemia, evidence of kidney dis- ease) or have resistant hypertension (not at target goal despite the use ofthree antihypertensive agents, including a diuretic).

Secondary hypertension. Most patients with established hypertension have primary hypertension. Consider secondary hyper- tension in patients who have atypical clinical features (ear$ onset, absent family history hypokalemia, evidence of kidney dis- ease) or have resistant hypertension (not at target goal despite the use ofthree antihypertensive agents, including a diuretic). STUDY TABLE: Selected Secondary Causes of Hypertension Condition Notes Drug induced NSAlDs, amphetamines/cocaine, sympathomimetics, oral contraceptives, glucocorticoids CKD Elevated BUN, serum creatinine, and potassium Renovascular disease Onset of hypertension at young age, especially in women (fibromuscular); atherosclerotic disease often (atherosclerotic and associated with cigarette smoking, flash pulmonary edema, CAD, flank bruits, advanced retinopathy, fibromuscular) increased creatinine (usually with bilateral renovascular disease), and increased creatinine after treatment with an ACE inhibitor or ARB (Continued on the nert page) 270

Nephrology SrUDY TAELE: Selected Secondary Causes of Hypertension (Continued) Condition Notes Primary hyperaldosteronism Muscle cramping, nocturia, thirst; physical examination normal; hypokalemia (50%) and elevated plasma aldosterone-plasma renin activity ratio Cushing syndrome Weight gain, menstrual irregularity, hirsutism; truncal obesity, abdominal striae; hypokalemia, metabolic alkalosis Pheoch romocytoma Sweating, pounding headache; pallor; tachycardia; hypertension may be episodic with intervals of normal BP; increased urine or plasma catecholamines or metanephrine DOil'T BETNICKED o Do not use plasma renin activity to risk stratifu patients with hypertension or to predict response to specific drugs. TESTYOURSELF A 3S-year-old woman is evaluated for persistent fatigue and resistant hypertension. Serum potassium level is 3.3 mEq/L. ANSWER: For diagnosis, choose primary aldosteronism. For management, select measurement of plasma aldosterone plasma renin activity ratio. Testing Collect data on cardiovascular risk factors and possible underlying secondary causes. Initial evaluation includes: o laboratory testing for kidney function, fasting blood glucose, fasting lipid panel, serum potassium, and serum calcium o ECG o urinalysis and albumin-creatinine ratio Treatment STUDY TAELE; ACC/AHA Classification and Treatment of Blood Pressure BP Category Office-Based Readings Treatment BP Target (mm Hg) (mm Hg) Normal SBP <1 20 and DBP <80 NA NA Elevated BP SBP 120-129 and DBP <80 Nonpharmacologic therapy (NPT) SBP <1 20 and DBP <80 Hypertension, stage 1 SBP 1 30-1 39 or DBP 80-89 NPT if 1 O-year ASCVD risk <1 0% <1 30/80 NPT + first-line drugs if clinical CV disease or 10-yearASCVD risk>10%

Elevated BP SBP 120-129 and DBP <80 Nonpharmacologic therapy (NPT) SBP <1 20 and DBP <80 Hypertension, stage 1 SBP 1 30-1 39 or DBP 80-89 NPT if 1 O-year ASCVD risk <1 0% <1 30/80 NPT + first-line drugs if clinical CV disease or 10-yearASCVD risk>10% Hypertension, stage 2 SBP >1 40 or DBP >90 Two first-line drugs of different classes, preferably <1 30/80 with once-daily dosing, if BP 20/10 mm Hg above target First-line antihypertensive agents are those shown to reduce clinical events. : ; For hypertension in the non-Black population, older adults, and patients with diabetes without albuminuria: . thiazide diuretic i t I . CCB I . ACE inhibitor or ARB t I For patients with diabetes and albuminuria: I L o ACE inhibitor or ARB t t 271 I t

Nephrology For patients with stage G3 kidney disease or higher or proteinuric kidney disease (urine albumin-creatine ratio >300 mg/g): r ACE inhibitor or ARB For stage t hypertension in the Black population without CKD or HF and with or without diabetes (but no albuminuria) o thiazide diuretic . CCB For patients with stage 2 hypertension, including Black patients: . combination of two first line antihypertensive drugs of different classes (except ACE inhibitors and ARBs) DOil'T BE TRICKED . Thiazide diuretics are not effective in patients with kidney disease (GFR <30 ml/min/1.73 m2l; select a loop diuretic. Renovascu la r Hypertension Testing Routine testing for renovascular disease in older patients with ASCVD is not recommended. In young women with resistant hypertension and a high clinical suspicion for fibromuscular dysplasia, renal artery imaging may be considered: . renal duplex Doppler ultrasonography . MRA or CTA (most accurate, but avoid in severe CKD) Treatment Renal artery angioplasty is no better than medical therapy in patients with atherosclerotic renovascular disease and stable kidney function. Therapy is directed at controlling ASCVD risk factors. In young persons with flbromuscular dysplasia, angioplasty may improve BP and cure hypertension. Hypertensive Urgency The treatment of hypertensive urgency (BP >180/120 mm Hg in the absence of symptoms or progressive target-organ damage) differs ifthe patient has previously treated hypertension or untreated hypertension. Systolic BP should be lowered no more than2S% within the first hour, then to <160/100 mm Hg within the next 2 to 6 hours, then cautiously to target during the following 24 to 48 hours. In patients with preexisting treated hypertension: . slowly restart the medication(s) in nonadherent patients. . in adherent patients, either increase the dose of the medication(s) or add an additional agent. In patients with previously untreated hypertension: . consider oral furosemide or small doses of clonidine or captopril and observe for several hours for a BP drop of 20 to 30 mm Hg (not to normal BP). o begin a long acting agent; discharge home with follow-up in 2 to 3 days. 272

Nephrology Hypertensive Emergency Hospitalize a patient with hypertensive emergency (BP >lB0/120 mm Hg and symptoms or evidence of end-organ damage). For a compelling condition (such as aortic dissection, severe preeclampsia or eclampsia, or pheochromocytoma crisis), SBp should be reduced to <140 mm Hg during the first hour and to <120 mm Hg in aortic dissection. Without a compelling condition, SBP should be reduced by no more than 25'l. within the first hour; then, if stable, reduce to 160/100 mm Hgwithin the next 2 to 6 hours; finally, cautiously reduce to normal during the following 24to 48 hours. See Neurologr for treatment of hypertension associated with ischemic stroke and intracerebral hemorrhage. For patients without a compelling indication, treatment consists of short-acting IV drugs administered in the ICU (e.g., nitro, glycerin, nitroprusside, labetalol, nicardipine). STUnY Y-AE*S: lVAntihypertensive Drugs forTreatment of Hypertensive Emergencies in Patients With a Compelling Comorbidity Comorbidity Preferred Drugs Acute aortic dissection Esmolol, labetalol Acute pulmonary edema Nitroglycerin, nitroprusside B-Blockers contraindicated ACS Esmolol, nitroglycerin AKI Nicardipine Eclampsia or preeclampsia Hydralazine, labetalol, nicardipine ACE inhibitors, ARBs, renin inhibitors, nitroprusside contraindicated. DOil'T BE TRIGKED o Do not select sublingual nifedipine for either hypertensive urgency or emergency Hypertension in Pregnancy Diagnosis Chronic hypertension in pregnancy. Hypertension before the 20th week of gestation is most consistent with previously undi- agnosed ch ronic hypertension.

DOil'T BE TRIGKED o Do not select sublingual nifedipine for either hypertensive urgency or emergency Hypertension in Pregnancy Diagnosis Chronic hypertension in pregnancy. Hypertension before the 20th week of gestation is most consistent with previously undi- agnosed ch ronic hypertension. Gestational h5rpertension is hypertension that develops after 20 weeks of pregnancy without preexisting hypertension, pro- teinuria, or other end organ damage. Gestational hypertension is a risk factor for preeclampsia and the development of chronic t hypertension. ; Preeclampsia is new onset hypertension after 20 weeks of pregnancy with proteinuria. Eclampsia is the presence of general- ized, tonic clonic seizures in a woman with preeclampsia. i I L i L Treatment i Treatment of hypertension less than 160/110 mm Hg during pregnancy is controversial, and benefits of treatment have not been L i demonstrated. I t Drugs that may be used during pregnancy: L I . methyldopa I . labetalol I I . calcium channel blockers (e.g., long-acting nifedipine) I t 273 I I

Nephrology Antihypertensive medications absolutely contraindicated during pregnancy: . ACE inhibitors . ARBs . renin inhibitors Diuretics may induce oligohydramnios if initiated during pregnancy. Preeclampsia. Definitive treatment is delivery including induction of labor in women at or near term. In the event of a hyper- tensive crisis, maternal BP stabilization should occur before delivery even in urgent circumstances. DON'T BE TRICKED . Treatment ofgestational hypertension does not prevent the occurrence ofpreeclampsia or chronic hypertension. Glomerular Diseases Glomerular disease should be suspected when proteinuria and/or hematuria are seen on urinalysis. The most common distinction is usually made between the nephrotic syndromes and the nephritic syndromes, also referred to as GN. Some conditions may present with either or both patterns, and some may progress from one pattern to the other. The Nephrotic Syndrome Diagnosis The nephrotic syndrome is characterized by o urine protein excretion >3500 mg/24 h or a urine protein-creatinine ratio >3500 mg/g . hypoalbuminemia, edema, and hyperlipidemia may be present The nephrotic slmdrome may be primary or secondary to systemic diseases such as diabetes, infection, or autoimmune diseases.

The Nephrotic Syndrome Diagnosis The nephrotic syndrome is characterized by o urine protein excretion >3500 mg/24 h or a urine protein-creatinine ratio >3500 mg/g . hypoalbuminemia, edema, and hyperlipidemia may be present The nephrotic slmdrome may be primary or secondary to systemic diseases such as diabetes, infection, or autoimmune diseases. STUDY IABLE: Common Causes of the Nephrotic Syndrome Condition Clinical Associations Diagnosis Treatment Focal segmental Most common cause of nephrotic syndrome in Biopsy Glucocorticoids or calcineurin g lomerulosclerosis Black persons inhibitors "Collapsing" variety associated with HIV Associated with morbid obesity Membranous Most common cause of nephropathy in White Biopsy 30% spontaneously remit in nephropathy persons 12-24 mo.freat with RAS blockade, statins, and diuretics Positive antibody against phospholipase 42 receptor lf persistent: g ucocorticoids and I

STUDY IABLE: Common Causes of the Nephrotic Syndrome Condition Clinical Associations Diagnosis Treatment Focal segmental Most common cause of nephrotic syndrome in Biopsy Glucocorticoids or calcineurin g lomerulosclerosis Black persons inhibitors "Collapsing" variety associated with HIV Associated with morbid obesity Membranous Most common cause of nephropathy in White Biopsy 30% spontaneously remit in nephropathy persons 12-24 mo.freat with RAS blockade, statins, and diuretics Positive antibody against phospholipase 42 receptor lf persistent: g ucocorticoids and I cyclophosphamide, calcineurin Secondary causes include infection (hepatitis B inhibitors, or rituximab and C, malaria, syphilis), SLE, drugs (NSAlDs), cancer (solid tumors, lymphoma) Treat concurrent conditions in secondary membranous High propensity for thrombosis, especially nephropathy renalvein thrombosis Minimal change Most common cause of primary nephrotic Biopsy lnitial treatment consists of glomerulopathy syndrome in children glucocorticoids 10% of nephrotic syndrome in adults (Continued on the next page) 274

Nephrology S?UDY TABLE: Common Causes of the Nephrotic Syndrome (Continued) Condition Clinical Associations Diagnosis Treatment Diabetic kidney Most common secondary cause ofthe Clinical diagnosis Excellent BP and glucose control disease nephrotic syndrome and the most common (diabetes of long ACE inhibitors orARBs overall cause in adults duration, albuminuria, and evidence of other microvascular and/or macrovascu lar d isease) DON'T BE TRICKED . Nephrotic range proteinuria in a patient with diabetes but without microvascular (e.g., retinopathy) or macrovascular (e.g., CAD) disease is not caused by diabetes. Kidney biopsy is required for definitive diagnosis. Treatment Treatment ofthe consequences ofthe nephrotic syndrome should occur simultaneously with treatment of the specific cause (if nephrotic syndrome is secondary to an underlying condition): . statins for elevated lipid levels o anticoagulation for thrombotic complications (because of urinary loss of antithrombins) fat Droplet: Iypical "Maltese cross" appearance of a fat droplet under polarized light microscopy commonly found in the nephrotic syndrome. o low salt diet and loop diuretics for edema The Nephritic Syndrome Diagnosis The nephritic syndrome (glomerulonephritis) is associated with glomerular inflammation resulting in hematuria, proteinuria, and leukocytes in the urine sediment. The hallmark is the presence of dysmorphic erythrocytes and erythrocyte casts. Proteinuria is variable. Systemic findings may include edema, hypertension, and kidney failure'

The Nephritic Syndrome Diagnosis The nephritic syndrome (glomerulonephritis) is associated with glomerular inflammation resulting in hematuria, proteinuria, and leukocytes in the urine sediment. The hallmark is the presence of dysmorphic erythrocytes and erythrocyte casts. Proteinuria is variable. Systemic findings may include edema, hypertension, and kidney failure' l(;i' o*l .i* "*s "u -s ,t t r-",\ rt al, ), * w i., # '€ ? il ffi ei /\ r* @ q . 'ir 3, tr 3 ** 't I I $.* f. ** . l) '1a q (: .. €i .l , {t '_.j : a

l(;i' o*l .i* "*s "u -s ,t t r-",\ rt al, ), * w i., # '€ ? il ffi ei /\ r* @ q . 'ir 3, tr 3 ** 't I I $.* f. ** . l) '1a q (: .. €i .l , {t '_.j : a Glomerulonephritis: Erythrocyte casts consistent with glomerulonephritis. .r qr* & Dysmorphi( Erythrocytes: Erythrocytes with abn0rmal morphology seen in glo- merulonephritis, including those with "Mickey Mouse ears."

Glomerulonephritis: Erythrocyte casts consistent with glomerulonephritis. .r qr* & Dysmorphi( Erythrocytes: Erythrocytes with abn0rmal morphology seen in glo- merulonephritis, including those with "Mickey Mouse ears." 275

Nephrology DON'T BE TRICKED . The absence of erythrocyte casts does not rule out glomerulonephritis. STUDY TASLE: Categorization of Glomerulonephritis Based on lmmunofluorescence Microscopy Findings lmmunofluorescence Staining Pattern Granular Pauci-immune Linear Lupus nephritis ANCA-associated GN Anti-GBM antibody disease lnfection-related GN lgA nephropathy MPGN Cryoglobulinemic GN STUDY lA3!E: Categorization of Glomerulonephritis Based on Serum Complement Levels Low Serum C3 and/or C4 Levels Normal Serum C3 and C4 Levels Lupus nephritis lgA nephropathy lnfection-related GN ANCA-associated GN MPGN Anti-GBM antibody disease Cryoglobulinemic GN Rapidly progressive GN is a clinical syndrome characterized by evidence of GN with progression to kidney failure within weeks. Findings include oliguria, rising serum creatinine levels, macroscopic or microscopic hematuria, erythrocyte casts, and pro- teinuria. It may be associated with any cause of GN or may be idiopathic. Rapidly progressive GN is particularly common with anti-GBM antibody disease (in younger patients) and pauci-immune small vessel vasculitis (in older patients). Serologic testing (e.g., ANCA, anti GBM antibodies, antinuclear antibodies) aids in the diagnosis. Diagnosis is made by kidney biopsy. Anti-Glomerular Basement Membrane Antibody Disease Anti GBM disease is an autoimmune disorder caused by antibodies directed against type IV collagen. If pulmonary capillaries are involved, it causes pulmonary hemorrhage (Goodpasture syndrome). Anti-GBM disease presents as RPGN with lung involve ment in >50% ol patients. Findings include normal complement levels and elevated levels of anti GBM antibodies. Kidney biopsy shows proliferative GN with linear deposition of immunoglobulin. Treatment is cyclophosphamide and glucocorticoids, combined with plasmapheresis ANcA-Associated Glomeru lonephritis Kidney manifestations range from only hematuria to RPGN. Systemic symptoms may include arthritis, leukocytoclastic vascu litis (palpable purpura), and pulmonary disease (pulmonary infiltrate to pulmonary hemorrhage).

Treatment is cyclophosphamide and glucocorticoids, combined with plasmapheresis ANcA-Associated Glomeru lonephritis Kidney manifestations range from only hematuria to RPGN. Systemic symptoms may include arthritis, leukocytoclastic vascu litis (palpable purpura), and pulmonary disease (pulmonary infiltrate to pulmonary hemorrhage). More than 807, of patients with MPA or granulomatosis with polyangiitis are ANCA positive; granulomatosis with polyangiitis is associated with (PR3) ANCA, and MPA is associated with (MPO) ANCA. Complement levels are normal. Kidney biopsy shows absent or minimal staining with immunoglobulin. Induction therapy consists of glucocorticoids and ryclophosphamide (or rituximab) with plasmapheresis if alveolar damage is evident. lgA Nephropathy IgA nephropathy most commonly presents as asymptomatic microscopic hematuria (with or without proteinuria) or episodic gross hematuria coincident with a URI (synpharyngitic nephritis). lgA nephropathy may also present as an acute GN or RPGN, with variable degrees of AKI, hypertension, edema, proteinuria, and hematuria. 276

Nephrology Kidney biopsy shows glomerular IgA deposits on immunofluorescence. Complement levels are normal. Most patients have a benign course without treatment; patients with proteinuria and risk lactors for progression may benefit from ACE inhibitors or ARBs. I gA Vascu I itis (Henoch-Schtin lein Pu rpu ra) IgA vasculitis may present with the classic tetrad of rash, arthralgia, abdominal pain, and kidney disease. Kidney involvement is similar to IgA nephropathy, and other organ involvement may occur. Diagnosis is confirmed either by finding an IgA dominant leukocytoclastic vasculitis or by kidney biopsy, which shows lesions similar to IgA nephropathy. Complement levels are normal. Treatment of kidney disease includes glucocorticoids and, in cases of associated RPGN. cyclophosphamide. Lupus Nephritis Patients ffpically have extrarenal symptoms of SLE at the time of diagnosis of LN. ANA and anti double stranded antibodies are positive, and C3 and C4 complement levels are depressed. Classification and recommended treatment of LN is made after kidney biopsy: . Class I and II (minimal or proliferative mesangial) lesions require no specific therapy other than RAS blockade. . Class III and IV (focal and diffuse glomerular lesions) induction therapy consists of high-dose glucocorticoids and either IV cyclophosphamide or mycophenolate mofetil (less toxic). . Class V (membranous) LN has a course similar to idiopathic membranous nephropathy, and induction therapy consists of glucocorticoids and IV cyclophosphamide, cyclosporine or tacrolimus, or mycophenolate mofetil (less toxic). I nfection-Related Glomeru lonephritis Staphylococcal infection is as common as or more common than streptococcal infection as a cause of infection-related GN. The clinical manifestations of poststreptococcal GN typically occur after a latent period of 1 to 6 weeks (check antistreptolysin O, anti-DNase titers) but may occur at the time of infection with other infectious agents. The presentation of inlection-related GN ranges from asymptomatic microscopic hematuria to RPGN. Diagnosis is clinical in nephritic patients who have an ongoing or preceding inf'ection. Complement levels are low. Treatment focuses on the underlying infection.

I nfection-Related Glomeru lonephritis Staphylococcal infection is as common as or more common than streptococcal infection as a cause of infection-related GN. The clinical manifestations of poststreptococcal GN typically occur after a latent period of 1 to 6 weeks (check antistreptolysin O, anti-DNase titers) but may occur at the time of infection with other infectious agents. The presentation of inlection-related GN ranges from asymptomatic microscopic hematuria to RPGN. Diagnosis is clinical in nephritic patients who have an ongoing or preceding inf'ection. Complement levels are low. Treatment focuses on the underlying infection. Membranoprol iferative G lomeruloneph ritis MPGN manifests in children or young adults as proteinuria or the nephrotic syndrome. Two forms exist: an immune-complex form mediated by antigen-antibody interactions triggering the classic complement pathway and a complement mediated form caused by a hyperactive alternative complement pathway. It is associated with immune complex disease (SLE), infections (HCV), and monoclonal gammopathy. Complement levels are low. Diagnosis and distinction of the two types are made by kidney biopsy and immunofluorescence microscopy. Treatment of MPGN includes immunosuppression and treatment olany underlying cause' 277

Nephrology sTU5Y TABLE; Diagnostic Findings in AKI Condition BUN-Creatinine Urine Osmolality Urine Sodium FEx. Urinalysis and Microscopy Ratio (mOsm/kg H2O) (mEq/t) Prerenal >20:1 >500 <20 <1Y" Specific gravity >1.020; normal or hyaline casts ATN 1 0:1 -300 >40 >2o/"' Specific gravity - 1.010; muddy brown casts and tubular epithelial cells AIN Variable Variable Variable Variable Mild proteinuria; leukocytes; erythrocytes; leukocyte casts; + eosinophiluria Acute GN Variable Variable Variable Variable Proteinuria; dysmorphic erythrocytes; erythrocyte casts Postrenal >20:1 Variable Variable Variable Variable, bland "FEN" may be low in contrast nephropathy and pigment nephropathy. FEy, may be >2"/,, in prerenal patients who are taking diuretics. In the setting of diuretics, the FEu,.,, calculated os (ULhg2 x P6,,)/(U6. x PLr,",) x 100, is more accurate in detecting volume-depleted states and prerenal AKI. FEu."" <35'X, is consistent with a prerenal cause olAKI. Knowing a few basic epidemiologic facts can help identify the cause of AKI:

FEy, may be >2"/,, in prerenal patients who are taking diuretics. In the setting of diuretics, the FEu,.,, calculated os (ULhg2 x P6,,)/(U6. x PLr,",) x 100, is more accurate in detecting volume-depleted states and prerenal AKI. FEu."" <35'X, is consistent with a prerenal cause olAKI. Knowing a few basic epidemiologic facts can help identify the cause of AKI: o Prerenal AKI is the most common form of AKI in the outpatient setting. I . A prolonged prerenal state may lead to ATN. r The most common cause of hospital-acquired AKI is ATN. . Hospital acquired ATN is most commonly caused by toxins, such L* Muddy Brown Granular Casts: Muddy brown granular casts consistent as antibiotics (i.e., gentamicin). with kidney injury secondary to tubular necrosis. o Obstruction of the upper tract (ureters or renal pelvis) must be bilateral to cause AKL

o Prerenal AKI is the most common form of AKI in the outpatient setting. I . A prolonged prerenal state may lead to ATN. r The most common cause of hospital-acquired AKI is ATN. . Hospital acquired ATN is most commonly caused by toxins, such L* Muddy Brown Granular Casts: Muddy brown granular casts consistent as antibiotics (i.e., gentamicin). with kidney injury secondary to tubular necrosis. o Obstruction of the upper tract (ureters or renal pelvis) must be bilateral to cause AKL gTUAY TABLE: Differential Diagnosis of AKI When you see this... Think of... And select.. Minimal proteinuria, no hematuria or ATN FEp" and/or spot urine sodium pyuria; presence of muddy brown casts Erythrocytes, erythrocyte casts, or GN As appropriate: dysmorph ic eryth rocytes Titers for ANA, anti-dsDNA antibodies, and antistreptolysin O antibodies; C3, C4, and CHro; hepatitis and HlVtesting and cryoglobulins; p-ANCA,/c- ANCA and anti-GBM antibodies ! fouria $relonephritis Urine culture AIN Review of medication list Eosinophilia, eosinophiluria, and rash AIN Review of medication list :

gTUAY TABLE: Differential Diagnosis of AKI When you see this... Think of... And select.. Minimal proteinuria, no hematuria or ATN FEp" and/or spot urine sodium pyuria; presence of muddy brown casts Erythrocytes, erythrocyte casts, or GN As appropriate: dysmorph ic eryth rocytes Titers for ANA, anti-dsDNA antibodies, and antistreptolysin O antibodies; C3, C4, and CHro; hepatitis and HlVtesting and cryoglobulins; p-ANCA,/c- ANCA and anti-GBM antibodies ! fouria $relonephritis Urine culture AIN Review of medication list Eosinophilia, eosinophiluria, and rash AIN Review of medication list : Cholesterol emboli lnvestigation for previous vascular procedure (angiography) Livedo reticularis (violaceous reticular rash) Cholesterol emboli Investigation for previous vascular procedure :

Cholesterol emboli lnvestigation for previous vascular procedure (angiography) Livedo reticularis (violaceous reticular rash) Cholesterol emboli Investigation for previous vascular procedure : (angiography) t Vasculitis I Consider cryoglobulinemia ''l Hypercalcemia and anemia Multiple myeloma Serum and urine protein electrophoresis, quantitative immunoglobulins : (Continued on the next page) : 280 I l '1 l

Nephrology STUOY ?&8lE: Differential Diagnosis of AKI (Continued) When you see this. Think of... And select... Nephrotic syndrome Diabetes mellitus Plasma glucose Renal vein thrombosis Renal vein Doppler study Obstruction on kidney ultrasound BPH Residual bladder volume, noncontrast CT or MRI Nephrolithiasis Obstructing malignant mass Retroperitoneal fibrosis Complete anuria Renal cortical necrosis Kidney ultrasonography Large kidneys on ultrasound Amyloidosis, diabetes (early), SPEP, blood glucose, HlVtesting HIV nephropathy Kidney failure following colonoscopy Phosphate-containing bowel Supportive care (fluids, stop ACE inhibitors, ARBs, prep (acute calcium NSAIDS) phosphate crystal deposition in the kidneys)

STUOY ?&8lE: Differential Diagnosis of AKI (Continued) When you see this. Think of... And select... Nephrotic syndrome Diabetes mellitus Plasma glucose Renal vein thrombosis Renal vein Doppler study Obstruction on kidney ultrasound BPH Residual bladder volume, noncontrast CT or MRI Nephrolithiasis Obstructing malignant mass Retroperitoneal fibrosis Complete anuria Renal cortical necrosis Kidney ultrasonography Large kidneys on ultrasound Amyloidosis, diabetes (early), SPEP, blood glucose, HlVtesting HIV nephropathy Kidney failure following colonoscopy Phosphate-containing bowel Supportive care (fluids, stop ACE inhibitors, ARBs, prep (acute calcium NSAIDS) phosphate crystal deposition in the kidneys) Recent abdominal surgery, hemorrhage, Abdominal compartment lntravesicular pressure >20 mm Hg or acute pancreatitis syndrome Peripheral blood smear schistocytes, Thrombotic microangiopathy As indicated, CBC, coagulation parameters thrombocytopenia (HUSffiP, DlC, scleroderma renal crisis) Urine dipstick positive for blood, no Hemolysis, rhabdomyolysis Serum CK, serum haptoglobin, reticulocyte count, erythrocytes on urinalysis peripheral blood smear AKI associated with acute leukemia or Tumor lysis syndrome Uric acid, phosphorus, potassium (all elevated) lymphoma or its treatment Worsening kidney function in the setting Cardiorenal syndrome Diuretics, ACE inhibitors orARBs, vasodilators, and of diuretic-resistant HF inotropes for improved cardiac function Worsening kidney function in setting of Hepatorenal syndrome lV albumin and intravascular volume repletion. Liver cirrhosis and ascites transplantation (see Gastroenterology and Hepatology, Cirrhosis)

Recent abdominal surgery, hemorrhage, Abdominal compartment lntravesicular pressure >20 mm Hg or acute pancreatitis syndrome Peripheral blood smear schistocytes, Thrombotic microangiopathy As indicated, CBC, coagulation parameters thrombocytopenia (HUSffiP, DlC, scleroderma renal crisis) Urine dipstick positive for blood, no Hemolysis, rhabdomyolysis Serum CK, serum haptoglobin, reticulocyte count, erythrocytes on urinalysis peripheral blood smear AKI associated with acute leukemia or Tumor lysis syndrome Uric acid, phosphorus, potassium (all elevated) lymphoma or its treatment Worsening kidney function in the setting Cardiorenal syndrome Diuretics, ACE inhibitors orARBs, vasodilators, and of diuretic-resistant HF inotropes for improved cardiac function Worsening kidney function in setting of Hepatorenal syndrome lV albumin and intravascular volume repletion. Liver cirrhosis and ascites transplantation (see Gastroenterology and Hepatology, Cirrhosis) TESTYOURSELF A 65-year old man develops eosinophilia, AKI, and a net-like rash on his lower extremities following a cardiac catheterization. ANSWER: For diagnosis, choose atheroembolic disease with cholesterol emboli to the skin and kidney. A 3S-year old woman with necrotizing pancreatitis and tense ascites develops AKI. ANSWER: For diagnosis, choose abdominal compartment syndrome; for management, choose measurement of intravesicular pressure. Treatment Begin IV 0.9% saline for patients with volume depletion. Stop potential nephrotoxic drugs and look particularly for aminogly- coside antibiotics, ACE inhibitors, ARBs, loop diuretics, SGLI2 inhibitors (volume depletion), cyclosporine, and NSAIDs. Select dialysis for:

A 3S-year old woman with necrotizing pancreatitis and tense ascites develops AKI. ANSWER: For diagnosis, choose abdominal compartment syndrome; for management, choose measurement of intravesicular pressure. Treatment Begin IV 0.9% saline for patients with volume depletion. Stop potential nephrotoxic drugs and look particularly for aminogly- coside antibiotics, ACE inhibitors, ARBs, loop diuretics, SGLI2 inhibitors (volume depletion), cyclosporine, and NSAIDs. Select dialysis for: . refractory hyperkalemia, acidemia, or volume overload . signs or symptoms of uremia (altered mentation, asterixis, pericardial friction rub, vomiting) . certain drug intoxications For urinary obstruction, choose a catheter to relieve bladder outlet obstruction. If the obstruction is above the bladder, select retrograde or antegrade nephrostomies. 281

Nephrology DOil'T BE TRICKED o Do not withhold dialysis until BUN, creatinine, or both reach "threshold" values. STUDY TABLE: AKI Treatment Protocol lndication Treatment Severe acidemia (pH <7.20) lV bicarbonate or hemodialysis Severe hypertension Vasodilators, B-blockers, calcium channel blockers Rapidly progressive GN, granulomatosis with polyangiitis, lm m u nosuppression and severe lgA nephropathy Scleroderma renal crisis ACE inhibitor, regardless of serum creatinine level and even if administering hemodialysis Hydronephrosis on ultrasound Depending on cause, bladder catheter or nephrostomy tube Abdominal compartment syndrome Su rgical decompression DON'T BE TRICKED . Do not select loop diuretics (without evidence of volume overload), dopamine, or mannitol to treat AKI. Contrast-Associated Neph ropathy Prevention In patients at high risk requiring imaging with contrast, avoid volume depletion and NSAIDs. Patients at high risk include those with recent AKI and those with eGFR <30 ml/min/l.73 m2. Prophylaxis with IV 0.97, saline is indicated for eGFR less <30 mL/ minl7.73 m2 or AKI. Diagnosis CAN is defined by an increase in serum creatinine within 24 to 48 hours following contrast exposure. AKI tends to be nonoligu ric, with an FEx, <1%. The urinary sediment may be bland or show classic ATN findings. DOil'T BE ?RICKED o Contrast induced nephropathy is not prevented by dialysis immediately after contrast media administration. o Do not use oral or intravenous acet5zlcysteine or IV bicarbonate to prevent AKI secondary to radiocontrast. Nephrolithiasis Diagnosis Kidney stones are predominantly composed of calcium but may be formed by other substrates, such as uric acid, struvite, and cystine. The classic symptoms of nephrolithiasis are acute flank pain with radiation to the groin and hematuria. Urinalysis usually reveals blood, and the urine sediment has nondysmorphic erythrocytes. Ultrasonography (indicated during pregnancy) or noncontrast CT is the preferred imaging choice.

Nephrolithiasis Diagnosis Kidney stones are predominantly composed of calcium but may be formed by other substrates, such as uric acid, struvite, and cystine. The classic symptoms of nephrolithiasis are acute flank pain with radiation to the groin and hematuria. Urinalysis usually reveals blood, and the urine sediment has nondysmorphic erythrocytes. Ultrasonography (indicated during pregnancy) or noncontrast CT is the preferred imaging choice. DOil'T BE TRICKED . The absence of erythroeytes on urinalysis does not rule out nephrolithiasis. 242

Nephrology Chronic Kidney Disease Screening Screening patients at risk for CKD, including those with diabetes, hypertension, and a family history of kidney disease, is gener- ally recommended. Diagnosis Diagnosis requires an eGFR <60 mL/min/1.73 m) confirmed at least 3 months after initial assessment, or persistent proteinuria or albuminuria regardless ol eGFR. Kidney biopsy is used to determine the cause of CKD when a glomerular or tubulointerstitial disease is Iikely and when specific therapy is available to delay or prevent further kidney injury. Kidney biopsy is not routinely performed in the presence of shrunken kidneys (<g cm), which generally indicate chronic irreversible disease. Differential diagnosis of CKD: o Diabetic kidney disease: Look for early moderately increased albuminuria (spot albumin-creatinine ratio, 30 300 mg/g), fbllowed by overt proteinuria, declining GFR, and a bland urine sediment. The presence of retinopathy strongly suggests coexisting diabetic kidney disease. . Glomerular disease: Look for glomerular hematuria, proteinuria, and hypertension, often with other systemic manifesta tions (LN and postinfectious GN). If nephrotic syndrome is present, look for focal segmental glomerulosclerosis, membra nous nephropathy, and minimal change disease. . Tubulointerstitial disease: Look for proteinuria, glycosuria, concentrating defect, sterile pyuria, and leukocyte casts, as well as papillary necrosis on ultrasound. Consider analgesic nephropathy (medication use, papillary necrosis), infection (TB, legionnaires disease, leptospirosis), allergic drug reaction (eosinophilia, eosinophiluria), autoimmune disorder (SLE, sarcoidosis, Sjdgren syndrome), and lead nephropathy (occupational exposure). . Vascular disease: Look for hematuria, proteinuria, and associated systemic illness. Vasculitis often presents with RPGN and palpable purpura (leukocytoclastic vasculitis). e After transplantation: CKD in the kidney transplant recipient may be caused by chronic allograft nephropathy. drug toxic ity (cyclosporine), polyomavirus BK infection, or recurrence of disease. o Structural disease (polycystic kidney disease): Look for hypertension, hematuria, palpable kidneys (advanced disease), and family history of CKD.

o Diabetic kidney disease: Look for early moderately increased albuminuria (spot albumin-creatinine ratio, 30 300 mg/g), fbllowed by overt proteinuria, declining GFR, and a bland urine sediment. The presence of retinopathy strongly suggests coexisting diabetic kidney disease. . Glomerular disease: Look for glomerular hematuria, proteinuria, and hypertension, often with other systemic manifesta tions (LN and postinfectious GN). If nephrotic syndrome is present, look for focal segmental glomerulosclerosis, membra nous nephropathy, and minimal change disease. . Tubulointerstitial disease: Look for proteinuria, glycosuria, concentrating defect, sterile pyuria, and leukocyte casts, as well as papillary necrosis on ultrasound. Consider analgesic nephropathy (medication use, papillary necrosis), infection (TB, legionnaires disease, leptospirosis), allergic drug reaction (eosinophilia, eosinophiluria), autoimmune disorder (SLE, sarcoidosis, Sjdgren syndrome), and lead nephropathy (occupational exposure). . Vascular disease: Look for hematuria, proteinuria, and associated systemic illness. Vasculitis often presents with RPGN and palpable purpura (leukocytoclastic vasculitis). e After transplantation: CKD in the kidney transplant recipient may be caused by chronic allograft nephropathy. drug toxic ity (cyclosporine), polyomavirus BK infection, or recurrence of disease. o Structural disease (polycystic kidney disease): Look for hypertension, hematuria, palpable kidneys (advanced disease), and family history of CKD. DOil'T BE TRTCKED . If the kidneys are markedly scarred and small (<9 cm), do not select aggressive diagnostic or therapeutic measures. Complications Many patients with CKD are asymptomatic. When CKD progresses to ESKD, uremic symptoms, such as fatigue, nausea, loss of appetite, insomnia, irritabiliry difficulty concentrating, confusion, or pruritus, may occur. Uremia may also induce pleuritis and pericarditis. Cardiovascular disease is the leading cause of death in patients with CKD. Chronic anemia, metabolic acidosis, and bone disease are also common complications. Renal osteodystrophy refers to alteration of bone morphologr in patients as a result of CKD.

Complications Many patients with CKD are asymptomatic. When CKD progresses to ESKD, uremic symptoms, such as fatigue, nausea, loss of appetite, insomnia, irritabiliry difficulty concentrating, confusion, or pruritus, may occur. Uremia may also induce pleuritis and pericarditis. Cardiovascular disease is the leading cause of death in patients with CKD. Chronic anemia, metabolic acidosis, and bone disease are also common complications. Renal osteodystrophy refers to alteration of bone morphologr in patients as a result of CKD. Acquired cystic kidney disease is common among patients with severe CKD and ESKD. These cysts are at increased risk for transformation into renal cell carcinoma. A high index of suspicion is warranted for patients with new gross hematuria, unex_ plained llank pain, or persistently elevated hemoglobin levels. For cysts that are highly suspicious tbr malignancy, partial nephrectomy is indicated for less severe stages of CKD. For patients with advanced CKD or ESKD, radical nephrectomy is preferred. 284

Nephrology STUDY TABLE! Renal Osteodystrophy Condition Mechanism Characteristics Osteitis fi brosa cystica Secondary hyperparathyroidism Subperiosteal resorption of bone, most prominently at the phalanges Adynamic bone disease Suppressed levels of PTH because of chronic illness or lncreased risk for fractures; made worse with overly aggressive treatment with vitamin D analogues bisphosphonate therapy Osteomalacia Vitamin D deficiency Bone pain, fractures Treatment Avoicl exposure to kidr.rey toxins (coutrast agents. NSAIDs). Avoid gadolinium enhanced MRI because <lftl're risl< fbr nephrogenic systemic fibrclsis (greirtest risk in patients receiving dialysis). Begin restriction of sodiunl, potassiunl, and phosphorus. Avoid signiticant proteiu restriction. l)rug ar.rd alkali therapy is based or-r specific 1)ndings. In patients with CKD stages 3r to 5 not receiving dialysis: o l.o\ 1cr elerated pl.rosphorus levels kr'"trard the normal rauge but not into the normal range rvith cliet modificatiott attd phosphate bir-rders (sevelamer, Ianthanunr). o Restrictordonotusecalciullr basedphosphutebinders(calciumcarbonate,calciumacetate). o Avoicl hypercalcemia; mild and asynrptonratic hypocalcemia can be tolerated. . Avoid routine use ol calcitriol ancl vitarnin D rnakrgues to lower PTH levels. In patients receiving cli:rlysis. calcirnimetics. calcitriol. ur vitamir.r D analogues. or their combination. sl.rould be used to lolr,cr P'l H lcvels. 37UDY TAELE: Drug Therapyfor CKD lf you see this... Select. Hypertension BP target <130/80 mm Hg

o l.o\ 1cr elerated pl.rosphorus levels kr'"trard the normal rauge but not into the normal range rvith cliet modificatiott attd phosphate bir-rders (sevelamer, Ianthanunr). o Restrictordonotusecalciullr basedphosphutebinders(calciumcarbonate,calciumacetate). o Avoicl hypercalcemia; mild and asynrptonratic hypocalcemia can be tolerated. . Avoid routine use ol calcitriol ancl vitarnin D rnakrgues to lower PTH levels. In patients receiving cli:rlysis. calcirnimetics. calcitriol. ur vitamir.r D analogues. or their combination. sl.rould be used to lolr,cr P'l H lcvels. 37UDY TAELE: Drug Therapyfor CKD lf you see this... Select. Hypertension BP target <130/80 mm Hg ACE inhibitor or ARB for patients with stage G3 CKD or higher or for those with stage G1 or G2 CKD with albuminuria (albumin-creatinine ratio >300 mglg) Use a loop diuretic ratherthan a thiazide for GFR <30 mL/min /1.73 m2 Hyperlipidemia Statin therapy in all patients )50 years with non dialysis dependent CKD and in adults aged 1B-49 years with non-dialysis-dependent CKD and any one of the following: CAD, diabetes, previous ischemic stroke, or a>10"/o cardiovascular risk Do not treat patients receiving dialysis with statins (no benefit) An e m a Erythropoietin to maintain hemoglobin levels of 10-1 1 g/dl and iron to maintain iron stores (always check iron levels before starting erythropoietin and maintain transferrin saturation levels >30% and serum ferritin levels >500 nglmL) Metabolic acidosis Start alkali therapy when IHCO3] is <22 mEg/L and maintain in normal range DON'T BE TRICKED . The anemia of CKD is a diagnosis ol exclusion. . I)o not use ACE ir.rhibitors in combination with ARBs or renin inhibitors to treat CKD patients with proteinuria. . I)o not use magnesium-containing antacids in patients with ESKD.

ACE inhibitor or ARB for patients with stage G3 CKD or higher or for those with stage G1 or G2 CKD with albuminuria (albumin-creatinine ratio >300 mglg) Use a loop diuretic ratherthan a thiazide for GFR <30 mL/min /1.73 m2 Hyperlipidemia Statin therapy in all patients )50 years with non dialysis dependent CKD and in adults aged 1B-49 years with non-dialysis-dependent CKD and any one of the following: CAD, diabetes, previous ischemic stroke, or a>10"/o cardiovascular risk Do not treat patients receiving dialysis with statins (no benefit) An e m a Erythropoietin to maintain hemoglobin levels of 10-1 1 g/dl and iron to maintain iron stores (always check iron levels before starting erythropoietin and maintain transferrin saturation levels >30% and serum ferritin levels >500 nglmL) Metabolic acidosis Start alkali therapy when IHCO3] is <22 mEg/L and maintain in normal range DON'T BE TRICKED . The anemia of CKD is a diagnosis ol exclusion. . I)o not use ACE ir.rhibitors in combination with ARBs or renin inhibitors to treat CKD patients with proteinuria. . I)o not use magnesium-containing antacids in patients with ESKD. TEST YOURSELF A 55 1'ear old u'oman u'ith chnrnic lor'ver back pain. polyLlria, ilnd noc turia is fbr-rnd kr hare CKD. Urinalysis shor,r,s no protein or erythrocytes. 5 to 10 leukocytes/hpt. ar.rd no casts. Urine culture shows no growth. Kidney ultrasound shows only papillary necrosis. l{ephrogenic Systemic Fibrosis: This patient with CKD developed ANSWER: For diagnosis, cl-roose tubulointcrstitial diseirse secondary to nephrogenic systemic fibrosis after an lt/Rl with gadolinium injection. The an;rlgesic irbuse. skin demonstrates erythema, edema, and a peau d'orange appL.r.r .c. 28s