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Acute Kidney Injury enzymatic activity and subsequent genetic testing. Screening for the disease is recommended for family members of affected Acute Kidney Injury patients. Enzyme replacement therapy with recombinant Definition human o-galactosidase A is available. Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function commonly accompanied by Apolipoprotein L1 Nephropathy decreased urine output, fluid retention, metabolic acidosis, Black persons develop kidney failure at rates four to five times hyperkalemia, and hyperphosphatemia. The Kidney higher than White persons. Genetic variants in the apolipo- Disease: Improving Global Outcomes (KDIGO) Acute Kidney protein L1 (APOL1) gene explain a large fraction of this health Injury Work Group definitions for AKI are described in disparity. Two risk alleles for kidney disease (G1 and G2) have Table 25. been identified in the APOL1 gene. The transmission of disease Multiple studies have showna correlation between more risk is consistent with recessive inheritance. High-risk APOL1 severe stages of AKI and higher mortality and health care uti- alleles are unusually prevalent possibly because they con- lization. Patients with AKI have an increased risk for develop- ferred a survival advantage in sub-Saharan Africa by enhanc- ing chronic kidney disease (CKD) and end-stage kidney ing innate immunity against African trypanosomal disease disease (ESKD). Likewise, patients with preexisting CKD are at (African sleeping sickness). an increased risk for developing AKI, a condition known as Persons with a high-risk APOL1 genotype have an approxi- acute-on-chronic kidney disease. mately 10-fold increased risk for focal segmental glomeruloscle- rosis, a 7-fold increased risk for hypertension-attributed ESKD, and, among those with HIV infection, a 29-fold increased risk e The Kidney Disease: Improving Global Outcomes (KDIGO) for HIV-associated nephropathy. In addition, the APOL1 risk Acute Kidney Injury Work Group defines acute kidney
enzymatic activity and subsequent genetic testing. Screening for the disease is recommended for family members of affected Acute Kidney Injury patients. Enzyme replacement therapy with recombinant Definition human o-galactosidase A is available. Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function commonly accompanied by Apolipoprotein L1 Nephropathy decreased urine output, fluid retention, metabolic acidosis, Black persons develop kidney failure at rates four to five times hyperkalemia, and hyperphosphatemia. The Kidney higher than White persons. Genetic variants in the apolipo- Disease: Improving Global Outcomes (KDIGO) Acute Kidney protein L1 (APOL1) gene explain a large fraction of this health Injury Work Group definitions for AKI are described in disparity. Two risk alleles for kidney disease (G1 and G2) have Table 25. been identified in the APOL1 gene. The transmission of disease Multiple studies have showna correlation between more risk is consistent with recessive inheritance. High-risk APOL1 severe stages of AKI and higher mortality and health care uti- alleles are unusually prevalent possibly because they con- lization. Patients with AKI have an increased risk for develop- ferred a survival advantage in sub-Saharan Africa by enhanc- ing chronic kidney disease (CKD) and end-stage kidney ing innate immunity against African trypanosomal disease disease (ESKD). Likewise, patients with preexisting CKD are at (African sleeping sickness). an increased risk for developing AKI, a condition known as Persons with a high-risk APOL1 genotype have an approxi- acute-on-chronic kidney disease. mately 10-fold increased risk for focal segmental glomeruloscle- rosis, a 7-fold increased risk for hypertension-attributed ESKD, and, among those with HIV infection, a 29-fold increased risk e The Kidney Disease: Improving Global Outcomes (KDIGO) for HIV-associated nephropathy. In addition, the APOL1 risk Acute Kidney Injury Work Group defines acute kidney genotype is associated with an increased risk for progression to injury by any of the following: increase in serum creati-
enzymatic activity and subsequent genetic testing. Screening for the disease is recommended for family members of affected Acute Kidney Injury patients. Enzyme replacement therapy with recombinant Definition human o-galactosidase A is available. Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function commonly accompanied by Apolipoprotein L1 Nephropathy decreased urine output, fluid retention, metabolic acidosis, Black persons develop kidney failure at rates four to five times hyperkalemia, and hyperphosphatemia. The Kidney higher than White persons. Genetic variants in the apolipo- Disease: Improving Global Outcomes (KDIGO) Acute Kidney protein L1 (APOL1) gene explain a large fraction of this health Injury Work Group definitions for AKI are described in disparity. Two risk alleles for kidney disease (G1 and G2) have Table 25. been identified in the APOL1 gene. The transmission of disease Multiple studies have showna correlation between more risk is consistent with recessive inheritance. High-risk APOL1 severe stages of AKI and higher mortality and health care uti- alleles are unusually prevalent possibly because they con- lization. Patients with AKI have an increased risk for develop- ferred a survival advantage in sub-Saharan Africa by enhanc- ing chronic kidney disease (CKD) and end-stage kidney ing innate immunity against African trypanosomal disease disease (ESKD). Likewise, patients with preexisting CKD are at (African sleeping sickness). an increased risk for developing AKI, a condition known as Persons with a high-risk APOL1 genotype have an approxi- acute-on-chronic kidney disease. mately 10-fold increased risk for focal segmental glomeruloscle- rosis, a 7-fold increased risk for hypertension-attributed ESKD, and, among those with HIV infection, a 29-fold increased risk e The Kidney Disease: Improving Global Outcomes (KDIGO) for HIV-associated nephropathy. In addition, the APOL1 risk Acute Kidney Injury Work Group defines acute kidney genotype is associated with an increased risk for progression to injury by any of the following: increase in serum creati- CKD in other nondiabetic kidney diseases, including lupus nine by 20.3 mg/dL (26.5 mol/L) within 48 hours; an nephritis and primary membranous nephropathy. increase in serum creatinine to 21.5 times baseline over 7 days; or a urine volume <0.5 mL/kg/h for 6 hours.
CKD in other nondiabetic kidney diseases, including lupus nine by 20.3 mg/dL (26.5 mol/L) within 48 hours; an nephritis and primary membranous nephropathy. increase in serum creatinine to 21.5 times baseline over 7 days; or a urine volume <0.5 mL/kg/h for 6 hours. ¢ Autosomal dominant tubulointerstitial kidney disease should be suspected in patients with slowly progressive chronic kidney disease, a bland urine sediment, small Epidemiology and kidneys, and a family history of end-stage kidney Pathophysiology disease. The incidence of AKI is estimated to be about 20% of all hospi- e Hereditary nephritis (Alport syndrome) is a glomerular tal admissions, of which approximately 10% require dialysis disease associated with sensorineural hearing loss and support. AKI affects >50% of patients in the ICU. Mortality characteristic ocular findings. varies depending on the severity of AKI, underlying cause, and e Thin glomerular basement membrane disease (benign patient population. Critically ill patients with AKI in the con- familial hematuria) results in hematuria without signif- text of multiorgan failure have been reported to have mortality icant proteinuria or ensuing glomerulosclerosis, with rates >50% when dialysis therapy is required.
e Thin glomerular basement membrane disease (benign patient population. Critically ill patients with AKI in the con- familial hematuria) results in hematuria without signif- text of multiorgan failure have been reported to have mortality icant proteinuria or ensuing glomerulosclerosis, with rates >50% when dialysis therapy is required. rare progression to chronic kidney disease. AKI can be divided into prerenal, intrinsic, and postre- nal causes and can be due to pharmacologic and nonphar- e High-risk APOL1 genotype confers increased risk for macologic causes (Table 26 and Table 27). Prerenal AKI chronic kidney disease in Black persons. (prerenal azotemia) is caused by decreased renal perfusion. TABLE 25. KDIGO Definition of Acute Kidney Injury? | Stage? Serum Creatinine Criteria Urine Output Criteria oe| | 1 Increase in Sc, to 1.5 to 1.9 times baseline within 7 days or 20.3 mg/dL <0.5 mL/kg/h for 6 to 12 h (26.5 umol/L) within 48 h
| Stage? Serum Creatinine Criteria Urine Output Criteria oe| | 1 Increase in Sc, to 1.5 to 1.9 times baseline within 7 days or 20.3 mg/dL <0.5 mL/kg/h for 6 to 12 h (26.5 umol/L) within 48 h Increase in Sc, to 2 to 2.9 times baseline <0.5 mL/kg/h for 212 h | Increase in Sc, to 3 times baseline or 24.0 mg/dL (353.6 mol/L) or initiation <0.3 mL/kg/h for 224 h or anuria for 212 h of RRT or, in patients <18 years, a decrease in eGFR to <35 mL/min/1.73 m? | eGFR = estimated glomerular filtration rate; KDIGO = Kidney Disease: Improving Global Outcomes; RRT = renal replacement therapy; Sc, = serum creatinine. | *The KDIGO definition is based on the RIFLE (Risk, Injury, Failure, Loss, and ESKD) and AKIN (Acute Kidney Injury Network) criteria. *The definition of acute kidney injury in any stage can be met by fulfilling either the serum creatinine criteria or the urine output criteria. Classification follows correction of volume status and relief of obstruction. 60
Acute Kidney Injury TABLE 26. Pharmacologic Causes of Acute Kidney Injury fot ause Examples Prerenal Volume depletion SGLT2 inhibitors, diuretics Intrarenal/afferent arteriolar NSAIDs (including COX-2 inhibitors); amphotericin B; calcineurin inhibitors; iodinated radiocontrast vasoconstriction agents Efferent arteriolar vasodilation Renin inhibitors; ACE inhibitors; ARBs | Intrinsic Acute tubular necrosis Aminoglycosides; vancomycin, particularly in combination with piperacillin-tazobactam; polymyxins; lithium; amphotericin B; pentamidine; cisplatin; foscarnet; tenofovir; cidofovir; carboplatin; ifosfamide; zoledronate; contrast agents; sucrose; immune globulins; mannitol; hydroxyethyl starch; dextran; synthetic cannabinoids; amphetamines Acute interstitial nephritis Etiologies of acute interstitial nephritis are similar to those for chronic tubulointerstitial nephritis. Acute interstitial nephritis may lead to chronic tubulointerstitial nephritis with protracted exposure (see Table 19) Acute glomerulonephritis ANCA-associated drugs, such as minocycline and levamisole (veterinary antihelmintic used in some cocaine preparations) Acute vascular syndromes Drug-induced TMA: quinine; cancer therapies (gemcitabine, mitomycin, bortezomib, sunitinib); | calcineurin inhibitors (cyclosporine, tacrolimus); drugs of abuse (cocaine, ecstasy, intravenous extended-release oxymorphone); clopidogrel; anti-angiogenesis drugs; interferon; mTOR inhibitors Intratubular obstruction Crystals: sulfonamides; triamterene; ciprofloxacin; ethylene glycol; acyclovir; indinavir; atazanavir; |
Acute vascular syndromes Drug-induced TMA: quinine; cancer therapies (gemcitabine, mitomycin, bortezomib, sunitinib); | calcineurin inhibitors (cyclosporine, tacrolimus); drugs of abuse (cocaine, ecstasy, intravenous extended-release oxymorphone); clopidogrel; anti-angiogenesis drugs; interferon; mTOR inhibitors Intratubular obstruction Crystals: sulfonamides; triamterene; ciprofloxacin; ethylene glycol; acyclovir; indinavir; atazanavir; | methotrexate; orlistat; large doses of vitamin C; sodium phosphate purgatives i | AKI =acute kidney injury; ARB = angiotensin receptor blocker; COX = cyclooxygenase; mTOR = mammalian target of rapamycin; SGLT2 = sodium-glucose cotransporter 2; TMA = thrombotic microangiopathy. | TABLE 27. Nonpharmacologic Causes of Acute Kidney Injury Cause Examples Prerenal Volume depletion Renal losses; Gl fluid losses; hemorrhage; burns | Decreased cardiac output Heart failure; massive pulmonary embolus; acute coronary syndrome Systemic vasodilation Sepsis; cirrhosis; anaphylaxis; anesthesia | Intrinsic Acute tubular necrosis Ischemic: prolonged prerenal AKI from hypovolemia, sepsis, or other causes of hypoperfusion Pigment: rhabdomyolysis; intravascular hemolysis Acute interstitial nephritis Etiologies of acute interstitial nephritis are similar to those for chronic tubulointerstitial nephritis. Acute interstitial nephritis may lead to chronic tubulointerstitial nephritis with protracted exposure (see Table 20) Acute glomerulonephritis Infection-related glomerulonephritis; cryoglobulinemia; IgA; lupus nephritis; renal vasculitis, including ANCA-associated; anti-GBM antibody disease Acute vascular syndromes — Macrovascular: renal artery occlusion; renal vein thrombosis; polyarteritis nodosa Microvascular:
Acute glomerulonephritis Infection-related glomerulonephritis; cryoglobulinemia; IgA; lupus nephritis; renal vasculitis, including ANCA-associated; anti-GBM antibody disease Acute vascular syndromes — Macrovascular: renal artery occlusion; renal vein thrombosis; polyarteritis nodosa Microvascular: Disease-associated TMA: HUS; atypical HUS; TTP; HELLP; scleroderma renal crisis; hypertensive emergency Atheroembolic disease Intratubular obstruction Paraprotein: myeloma; TLS Postrenal Upper tract obstruction Nephrolithiasis; blood clots; external compression | Lower tract obstruction BPH; neurogenic bladder; blood clots; cancer; urethral stricture AKI = acute kidney injury; ANCA = antineutrophil cytoplasmic antibody; BPH = benign prostatic hyperplasia; GBM = glomerular basement membrane; Gl = gastrointestinal; HELLP = | hemolysis, elevated liver enzymes, and low platelets; HUS = hemolytic uremic syndrome; TLS = tumor lysis syndrome; TMA = thrombotic microangiopathy; TTP = thrombotic thrombocytopenic purpura. Leese: 61
Acute Kidney Injury The integrity of renal tissue is preserved, and tubular and CKD is knowledge of previous serum creatinine levels; glomerular function remains normal. Intrinsic AKI is caused documentation of similarly elevated creatinine levels for by structural damage to the renal parenchyma. Postrenal 23 months suggests that the kidney failure is chronic. AKI refers to AKI caused by urinary tract obstruction. However, serum creatinine concentration can be increased Prerenal AKI and acute tubular necrosis (ATN) account for by multiple factors independent of kidney function, limiting approximately 65% to 75% of AKI cases in hospitalized its specificity for diagnosis of AKI. Serum creatinine is not a patients. sensitive marker of kidney injury in patients with sepsis, liver disease, muscle wasting, or fluid overload and does not provide any information regarding the cause of AKI. ¢ Prerenal acute kidney injury and acute tubular necrosis Moreover, the rise in serum creatinine is delayed 24 to account for approximately 65% to 75% of acute kidney 36 hours after the onset of injury and decline in glomerular injury cases in hospitalized patients. filtration rate (GFR). The history focuses on identifying vasoactive and poten- tial nephrotoxic medications (including over-the-counter Clinical Manifestations medications, herbal products, and recreational drugs); recent Patients with AKI can be asymptomatic until extreme loss of exposure to iodinated contrast agents; other predisposing kidney function occurs, and patients with mild to moderate conditions for AKI; and urinary obstructive symptoms (see AKI are often diagnosed by laboratory studies only. Patients Table 26 and Table 27). Physical examination focuses on blood with AKI can also present with oliguria (urine output pressure, heart rate, signs of volume status such as jugular <500 mL/d or <0.3 mL/kg/h) or anuria (urine output venous pressure level and skin turgor, and bladder percussion/ <50 mL/d). Severe AKI can lead to symptoms from volume palpation. Laboratory evaluation includes blood urea nitrogen overload, electrolyte abnormalities, and uremia. Acute uremic (BUN) and creatinine concentrations, electrolytes, complete symptoms include nausea, vomiting, anorexia, fatigue, mus- blood count, and assessment of the urine (urine indices, uri- cle cramps, restless legs, confusion, and pruritus. Physical nalysis, and microscopic evaluation of the urine sediment) signs may include asterixis. Other manifestations may be (Table 28 and Table 29). bleeding (due to platelet dysfunction), pericarditis, and sei- In patients with oliguria, the fractional excretion of zures. Drug or metabolite accumulation and toxicity may sodium (FEy,) or urea (FEyyeq) can help distinguish between complicate the course. prerenal AKI and ATN, with some caveats (see Table 28). Ultrasonography of the kidneys and bladder should be obtained to exclude urinary tract obstruction and when the e Patients with acute kidney injury (AKI) can be asymp- underlying cause of AKI is unclear. Kidney size may help dis- tomatic until extreme loss of kidney function occurs; tinguish between AKI and CKD, because diminished kidney severe AKI can lead to symptoms from volume overload, size with increased cortical echogenicity and/or thinning sug- electrolyte abnormalities, and uremia. gests CKD. Kidney size can be normal in patients with CKD from infiltrative disorders such as diabetes mellitus, HIV- associated nephropathy, amyloidosis, or multiple myeloma. Diagnosis Kidney biopsy should be considered in patients with AKI from The diagnosis of AKI is based on increased levels of serum no apparent cause, suspected glomerulonephritis, or unex- creatinine. The most reliable way to distinguish AKI from plained systemic disease.
The integrity of renal tissue is preserved, and tubular and CKD is knowledge of previous serum creatinine levels; glomerular function remains normal. Intrinsic AKI is caused documentation of similarly elevated creatinine levels for by structural damage to the renal parenchyma. Postrenal 23 months suggests that the kidney failure is chronic. AKI refers to AKI caused by urinary tract obstruction. However, serum creatinine concentration can be increased Prerenal AKI and acute tubular necrosis (ATN) account for by multiple factors independent of kidney function, limiting approximately 65% to 75% of AKI cases in hospitalized its specificity for diagnosis of AKI. Serum creatinine is not a patients. sensitive marker of kidney injury in patients with sepsis, liver disease, muscle wasting, or fluid overload and does not provide any information regarding the cause of AKI. ¢ Prerenal acute kidney injury and acute tubular necrosis Moreover, the rise in serum creatinine is delayed 24 to account for approximately 65% to 75% of acute kidney 36 hours after the onset of injury and decline in glomerular injury cases in hospitalized patients. filtration rate (GFR). The history focuses on identifying vasoactive and poten- tial nephrotoxic medications (including over-the-counter Clinical Manifestations medications, herbal products, and recreational drugs); recent Patients with AKI can be asymptomatic until extreme loss of exposure to iodinated contrast agents; other predisposing kidney function occurs, and patients with mild to moderate conditions for AKI; and urinary obstructive symptoms (see AKI are often diagnosed by laboratory studies only. Patients Table 26 and Table 27). Physical examination focuses on blood with AKI can also present with oliguria (urine output pressure, heart rate, signs of volume status such as jugular <500 mL/d or <0.3 mL/kg/h) or anuria (urine output venous pressure level and skin turgor, and bladder percussion/ <50 mL/d). Severe AKI can lead to symptoms from volume palpation. Laboratory evaluation includes blood urea nitrogen overload, electrolyte abnormalities, and uremia. Acute uremic (BUN) and creatinine concentrations, electrolytes, complete symptoms include nausea, vomiting, anorexia, fatigue, mus- blood count, and assessment of the urine (urine indices, uri- cle cramps, restless legs, confusion, and pruritus. Physical nalysis, and microscopic evaluation of the urine sediment) signs may include asterixis. Other manifestations may be (Table 28 and Table 29). bleeding (due to platelet dysfunction), pericarditis, and sei- In patients with oliguria, the fractional excretion of zures. Drug or metabolite accumulation and toxicity may sodium (FEy,) or urea (FEyyeq) can help distinguish between complicate the course. prerenal AKI and ATN, with some caveats (see Table 28). Ultrasonography of the kidneys and bladder should be obtained to exclude urinary tract obstruction and when the e Patients with acute kidney injury (AKI) can be asymp- underlying cause of AKI is unclear. Kidney size may help dis- tomatic until extreme loss of kidney function occurs; tinguish between AKI and CKD, because diminished kidney severe AKI can lead to symptoms from volume overload, size with increased cortical echogenicity and/or thinning sug- electrolyte abnormalities, and uremia. gests CKD. Kidney size can be normal in patients with CKD from infiltrative disorders such as diabetes mellitus, HIV- associated nephropathy, amyloidosis, or multiple myeloma. Diagnosis Kidney biopsy should be considered in patients with AKI from The diagnosis of AKI is based on increased levels of serum no apparent cause, suspected glomerulonephritis, or unex- creatinine. The most reliable way to distinguish AKI from plained systemic disease. TABLE 28. Diagnostic Findings Differentiating Prerenal Acute Kidney Injury From Acute Tubular Necrosis
The integrity of renal tissue is preserved, and tubular and CKD is knowledge of previous serum creatinine levels; glomerular function remains normal. Intrinsic AKI is caused documentation of similarly elevated creatinine levels for by structural damage to the renal parenchyma. Postrenal 23 months suggests that the kidney failure is chronic. AKI refers to AKI caused by urinary tract obstruction. However, serum creatinine concentration can be increased Prerenal AKI and acute tubular necrosis (ATN) account for by multiple factors independent of kidney function, limiting approximately 65% to 75% of AKI cases in hospitalized its specificity for diagnosis of AKI. Serum creatinine is not a patients. sensitive marker of kidney injury in patients with sepsis, liver disease, muscle wasting, or fluid overload and does not provide any information regarding the cause of AKI. ¢ Prerenal acute kidney injury and acute tubular necrosis Moreover, the rise in serum creatinine is delayed 24 to account for approximately 65% to 75% of acute kidney 36 hours after the onset of injury and decline in glomerular injury cases in hospitalized patients. filtration rate (GFR). The history focuses on identifying vasoactive and poten- tial nephrotoxic medications (including over-the-counter Clinical Manifestations medications, herbal products, and recreational drugs); recent Patients with AKI can be asymptomatic until extreme loss of exposure to iodinated contrast agents; other predisposing kidney function occurs, and patients with mild to moderate conditions for AKI; and urinary obstructive symptoms (see AKI are often diagnosed by laboratory studies only. Patients Table 26 and Table 27). Physical examination focuses on blood with AKI can also present with oliguria (urine output pressure, heart rate, signs of volume status such as jugular <500 mL/d or <0.3 mL/kg/h) or anuria (urine output venous pressure level and skin turgor, and bladder percussion/ <50 mL/d). Severe AKI can lead to symptoms from volume palpation. Laboratory evaluation includes blood urea nitrogen overload, electrolyte abnormalities, and uremia. Acute uremic (BUN) and creatinine concentrations, electrolytes, complete symptoms include nausea, vomiting, anorexia, fatigue, mus- blood count, and assessment of the urine (urine indices, uri- cle cramps, restless legs, confusion, and pruritus. Physical nalysis, and microscopic evaluation of the urine sediment) signs may include asterixis. Other manifestations may be (Table 28 and Table 29). bleeding (due to platelet dysfunction), pericarditis, and sei- In patients with oliguria, the fractional excretion of zures. Drug or metabolite accumulation and toxicity may sodium (FEy,) or urea (FEyyeq) can help distinguish between complicate the course. prerenal AKI and ATN, with some caveats (see Table 28). Ultrasonography of the kidneys and bladder should be obtained to exclude urinary tract obstruction and when the e Patients with acute kidney injury (AKI) can be asymp- underlying cause of AKI is unclear. Kidney size may help dis- tomatic until extreme loss of kidney function occurs; tinguish between AKI and CKD, because diminished kidney severe AKI can lead to symptoms from volume overload, size with increased cortical echogenicity and/or thinning sug- electrolyte abnormalities, and uremia. gests CKD. Kidney size can be normal in patients with CKD from infiltrative disorders such as diabetes mellitus, HIV- associated nephropathy, amyloidosis, or multiple myeloma. Diagnosis Kidney biopsy should be considered in patients with AKI from The diagnosis of AKI is based on increased levels of serum no apparent cause, suspected glomerulonephritis, or unex- creatinine. The most reliable way to distinguish AKI from plained systemic disease. TABLE 28. Diagnostic Findings Differentiating Prerenal Acute Kidney Injury From Acute Tubular Necrosis | Condition BUN-Creatinine Urine Osmolality Urine Sodium FEy,? FEy,ca” Urinalysis and Ratio (mOsm/kg H,O) (mEq/L [mmol/L]) Microscopy | | Prerenal >20:1 >500 <20 <1% -<35% ~— Specific gravity>1.020; | | ; normal or hyaline casts | | Acute tubular 10-15:1 ~300 >40 >2%4 >35% Specific gravity ~1.010; | | necrosis pigmented granular (muddy brown) casts and tubular epithelial cells | | | BUN = blood urea nitrogen; FE,, = fractional excretion of sodium; FEy,., = fractional excretion of urea.
| Condition BUN-Creatinine Urine Osmolality Urine Sodium FEy,? FEy,ca” Urinalysis and Ratio (mOsm/kg H,O) (mEq/L [mmol/L]) Microscopy | | Prerenal >20:1 >500 <20 <1% -<35% ~— Specific gravity>1.020; | | ; normal or hyaline casts | | Acute tubular 10-15:1 ~300 >40 >2%4 >35% Specific gravity ~1.010; | | necrosis pigmented granular (muddy brown) casts and tubular epithelial cells | | | BUN = blood urea nitrogen; FE,, = fractional excretion of sodium; FEy,., = fractional excretion of urea. || °FEy, = (Urine sodium concentration x Plasma creatinine concentration)/(Urine creatinine concentration x Plasma sodium concentration) x 100. || ®FEy.., = (Urine urea concentration x Plasma creatinine concentration)/(Urine creatinine concentration x Plasma urea concentration) x 100 i
|| °FEy, = (Urine sodium concentration x Plasma creatinine concentration)/(Urine creatinine concentration x Plasma sodium concentration) x 100. || ®FEy.., = (Urine urea concentration x Plasma creatinine concentration)/(Urine creatinine concentration x Plasma urea concentration) x 100 i | “FE,,, can be high in prerenal states with diuretic use, adrenal insufficiency, or metabolic alkalosis. | SFE,,, can be low in acute tubular necrosis due to contrast-associated nephropathy, pigment nephropathy, glomerulonephritis, or early obstruction. | } 62
Acute Kidney Injury TABLE 29. Urinalysis and Microscopy in Acute depletion. Drugs impairing vasodilatation of the afferent Kidney Injury arterioles (such as NSAIDs) or vasoconstriction of the efferent Condition Findings | arterioles (such as ACE inhibitors or angiotensin receptor blockers) can cause prerenal AKI, especially in the setting of Acute interstitial nephritis Mild proteinuria; leukocytes; | erythrocytes; leukocyte casts | volume depletion, decreased effective arterial circulation, or preexisting CKD. Calcineurin inhibitors such as cyclosporine Acute glomerulonephritis Proteinuria; dysmorphic erythrocytes; erythrocyte casts and tacrolimus can cause prerenal AKI from afferent arteri- Intratubular obstruction Crystalluria or Bence-Jones olar vasoconstriction. proteinuria? | Management of prerenal AKI includes discontinuing Acute vascular syndromes Variable hematuria; sometimes nephrotoxins and increasing renal perfusion by treating the mimics acute glomerulonephritis | underlying cause, such as correcting volume deficits. If prere- Postrenal Variable; bland nal AKI is not recognized and treated in a timely fashion, prolonged renal hypoperfusion can result in ATN and progres- *Detected by urine immunofixation. sive intrinsic kidney failure.
Postrenal Variable; bland nal AKI is not recognized and treated in a timely fashion, prolonged renal hypoperfusion can result in ATN and progres- *Detected by urine immunofixation. sive intrinsic kidney failure. e Prerenal acute kidney injury is caused by underperfu- sion of the kidney with a subsequent decrease in glo- e In patients with suspected acute kidney injury, physical merular filtration rate, which is reversible with discon- examination focuses on blood pressure, heart rate, signs tinuing nephrotoxins and treating the underlying cause. of volume status, and bladder percussion/palpation. e Renal hypoperfusion can occur due to intravascular vol- e Ultrasonography of the kidneys and bladder should be ume depletion, decreased effective arterial circulation, obtained for suspected urinary tract obstruction or when or renal vasoconstriction. the underlying cause of acute kidney injury is unclear. Intrinsic Kidney Diseases Causes Intrinsic AKI occurs from structural damage to the renal AKI can be divided into prerenal, intrinsic, and postrenal tubules, interstitium, glomerulus, or vascular structures, or causes. from intratubular obstruction (see Table 26 and Table 27).
Intrinsic Kidney Diseases Causes Intrinsic AKI occurs from structural damage to the renal AKI can be divided into prerenal, intrinsic, and postrenal tubules, interstitium, glomerulus, or vascular structures, or causes. from intratubular obstruction (see Table 26 and Table 27). Prerenal Acute Kidney Injury Acute Tubular Necrosis See Table 26 and Table 27 for the causes of prerenal AKI. ATN due to ischemia, nephrotoxins, and/or sepsis is the most Prerenal AKI (prerenal azotemia) is caused by underper- common cause of AKI in hospitalized patients. A history of fusion of the kidney with a subsequent decrease in GFR, sepsis, documented protracted hypotension, or nephrotoxin which is reversible with appropriate therapy. Renal hypoper- exposure along with assessment of hemodynamics and vol- fusion can occur due to intravascular volume depletion, ume status can aid in the diagnosis. Laboratory values sugges- decreased effective arterial circulation, renal vasoconstriction, tive of ATN are described in Table 28. Urine sediment may be and/or medications. Patients may have a history of acute hem- bland but is usually notable for the presence of tubular epithe- orrhage, loss of gastrointestinal fluids, heart failure, decom- lial cells and coarse granular (muddy brown) casts (Figure 18). pensated liver disease, sepsis, or recent diuretic or NSAID use. Unlike prerenal AKI, ATN does not rapidly improve with Physical signs of hypovolemia include hypotension, tachycar- restoration of intravascular volume and blood flow to the kid- dia, orthostasis, and decreased skin turgor. Patients with heart neys. Treatment is supportive because no efficacious pharma- failure or cirrhosis have physical examination findings sup- cologic therapies exist. Complete or partial renal recovery can porting these conditions. take days to weeks. Nonoliguric ATN portends a better renal In prerenal AKI, the kidney responds by reabsorbing urea, prognosis than oliguric ATN. Patients with advanced CKD are sodium, and water. Laboratory values that support a diagnosis less likely to recover kidney function compared with patients of prerenal AKI are listed in Table 28. Prerenal AKI due to with baseline normal kidney function or early CKD. Patients hypovolemia can be distinguished from ATN by the response with severe ATN who require acute dialysis often recover kid- to a volume challenge. Improvement in urine output (if oligu- ney function but may progress to dialysis-dependent ESKD. ric) and serum creatinine support the diagnosis of a prerenal etiology. Ischemic Acute Tubular Necrosis Drug-induced prerenal AKI typically results from Severe ischemia due to prolonged hypotension, protracted decreased blood flow to the kidney or intraglomerular prerenal state, or sepsis can cause ATN (see Table 27). The hemodynamic alterations. Sodium-glucose cotransporter-2 ischemic injury leads to cytokine release, oxygen-free radical inhibitors or diuretics can cause prerenal AKI from volume and enzyme production, endothelial activation and leukocyte
Prerenal Acute Kidney Injury Acute Tubular Necrosis See Table 26 and Table 27 for the causes of prerenal AKI. ATN due to ischemia, nephrotoxins, and/or sepsis is the most Prerenal AKI (prerenal azotemia) is caused by underper- common cause of AKI in hospitalized patients. A history of fusion of the kidney with a subsequent decrease in GFR, sepsis, documented protracted hypotension, or nephrotoxin which is reversible with appropriate therapy. Renal hypoper- exposure along with assessment of hemodynamics and vol- fusion can occur due to intravascular volume depletion, ume status can aid in the diagnosis. Laboratory values sugges- decreased effective arterial circulation, renal vasoconstriction, tive of ATN are described in Table 28. Urine sediment may be and/or medications. Patients may have a history of acute hem- bland but is usually notable for the presence of tubular epithe- orrhage, loss of gastrointestinal fluids, heart failure, decom- lial cells and coarse granular (muddy brown) casts (Figure 18). pensated liver disease, sepsis, or recent diuretic or NSAID use. Unlike prerenal AKI, ATN does not rapidly improve with Physical signs of hypovolemia include hypotension, tachycar- restoration of intravascular volume and blood flow to the kid- dia, orthostasis, and decreased skin turgor. Patients with heart neys. Treatment is supportive because no efficacious pharma- failure or cirrhosis have physical examination findings sup- cologic therapies exist. Complete or partial renal recovery can porting these conditions. take days to weeks. Nonoliguric ATN portends a better renal In prerenal AKI, the kidney responds by reabsorbing urea, prognosis than oliguric ATN. Patients with advanced CKD are sodium, and water. Laboratory values that support a diagnosis less likely to recover kidney function compared with patients of prerenal AKI are listed in Table 28. Prerenal AKI due to with baseline normal kidney function or early CKD. Patients hypovolemia can be distinguished from ATN by the response with severe ATN who require acute dialysis often recover kid- to a volume challenge. Improvement in urine output (if oligu- ney function but may progress to dialysis-dependent ESKD. ric) and serum creatinine support the diagnosis of a prerenal etiology. Ischemic Acute Tubular Necrosis Drug-induced prerenal AKI typically results from Severe ischemia due to prolonged hypotension, protracted decreased blood flow to the kidney or intraglomerular prerenal state, or sepsis can cause ATN (see Table 27). The hemodynamic alterations. Sodium-glucose cotransporter-2 ischemic injury leads to cytokine release, oxygen-free radical inhibitors or diuretics can cause prerenal AKI from volume and enzyme production, endothelial activation and leukocyte 63
Acute Kidney Injury and swelling of the renal proximal tubular cells with resultant tubular obstruction and damage. Contrast agents can cause nonoliguric ATN primarily through renal vasoconstriction and oxygen-free, radical- associated injury. The serum creatinine increases within 24 to 48 hours after contrast administration. Aminoglycosides cause nonoliguric ATN through direct tubular toxicity with an increase in serum creatinine occurring 5 to 7 days after initiation of therapy. Cisplatin causes ATN through direct tubular toxicity, renal vasoconstriction, and inflammation. Amphotericin B causes dose-related AKI through both renal vasoconstriction and direct tubular toxicity and may be asso- ciated with nephrogenic diabetes insipidus in addition to the aforementioned tubular defects. Lipid-based preparations decrease the risk for nephrotoxicity. Vancomycin nephrotoxic- ity occurs in the setting of high trough levels (>15 mg/L), high vancomycin dose (24 g/d), prolonged duration of therapy, and/ or concomitant nephrotoxic drugs, most notably an aminogly- coside or piperacillin-tazobactam. Certain types of synthetic cannabinoids used as recreational drugs have been associated with ATN.
and swelling of the renal proximal tubular cells with resultant tubular obstruction and damage. Contrast agents can cause nonoliguric ATN primarily through renal vasoconstriction and oxygen-free, radical- associated injury. The serum creatinine increases within 24 to 48 hours after contrast administration. Aminoglycosides cause nonoliguric ATN through direct tubular toxicity with an increase in serum creatinine occurring 5 to 7 days after initiation of therapy. Cisplatin causes ATN through direct tubular toxicity, renal vasoconstriction, and inflammation. Amphotericin B causes dose-related AKI through both renal vasoconstriction and direct tubular toxicity and may be asso- ciated with nephrogenic diabetes insipidus in addition to the aforementioned tubular defects. Lipid-based preparations decrease the risk for nephrotoxicity. Vancomycin nephrotoxic- ity occurs in the setting of high trough levels (>15 mg/L), high vancomycin dose (24 g/d), prolonged duration of therapy, and/ or concomitant nephrotoxic drugs, most notably an aminogly- coside or piperacillin-tazobactam. Certain types of synthetic cannabinoids used as recreational drugs have been associated with ATN. FIGURE 18. Urine sediment showing multiple coarse, granular (muddy brown) Pigment Nephropathy casts characteristic of acute tubular necrosis. Heme pigment released from myoglobin or hemoglobin can cause AKI through intravascular volume depletion (seen in adhesion, activation of coagulation, and apoptosis. GFR rhabdomyolysis), renal vasoconstriction, direct proximal declines because of renal vasoconstriction, tubular back leak tubular injury, and tubular obstruction. Urine heme pigment of filtrate into the bloodstream, and tubular obstruction from from myoglobin or hemoglobin causes a positive urine dip- sloughed cellular debris. stick for blood with the absence of erythrocytes on sediment Normotensive ischemic ATN can occur without overt examination.
FIGURE 18. Urine sediment showing multiple coarse, granular (muddy brown) Pigment Nephropathy casts characteristic of acute tubular necrosis. Heme pigment released from myoglobin or hemoglobin can cause AKI through intravascular volume depletion (seen in adhesion, activation of coagulation, and apoptosis. GFR rhabdomyolysis), renal vasoconstriction, direct proximal declines because of renal vasoconstriction, tubular back leak tubular injury, and tubular obstruction. Urine heme pigment of filtrate into the bloodstream, and tubular obstruction from from myoglobin or hemoglobin causes a positive urine dip- sloughed cellular debris. stick for blood with the absence of erythrocytes on sediment Normotensive ischemic ATN can occur without overt examination. hypotension in conditions with impaired renal autoregulation. In rhabdomyolysis, myoglobin is released in the circu- These conditions include older age, hypertension, atheroscle- lation from damaged skeletal muscle. Major causes of rhab- rotic or renovascular disease, and CKD. Patients with hyper- domyolysis include trauma, drugs and toxins, seizures, tension can develop normotensive ischemic ATN if their blood metabolic and electrolyte disorders, endocrinopathies (dia- pressure is decreased to a value lower than what they are betic ketoacidosis, hyperglycemic hyperosmolar syndrome, accustomed to but within normal range. Management involves hypothyroidism), and intense exercise, particularly in treating any volume deficits and decreasing antihypertensive poorly conditioned individuals. Rhabdomyolysis-induced medications to allow the blood pressure to increase to baseline AKI is more likely to occur with serum creatine kinase lev- levels. els >5000 U/L. In addition to elevated serum creatine kinase and serum creatinine levels, hyperkalemia, hypocalcemia, Drug-Induced Acute Tubular Necrosis hyperphosphatemia, hyperuricemia, metabolic acidosis, Drug-induced ATN can be a consequence of prolonged hemo- increased lactate dehydrogenase (LDH) concentration, and dynamic alterations or direct tubular injury (see Table 26). The increased aspartate and alanine aminotransferase levels can drugs associated with prerenal AKI can cause ATN from pro- occur. Urinary findings include FEy, <1% (due to renal vaso- longed hypoperfusion. Early recognition and prompt discon- constriction), myoglobinuria, and pigmented (red) granular tinuation of the drug are essential for renal recovery. The risk casts.
hypotension in conditions with impaired renal autoregulation. In rhabdomyolysis, myoglobin is released in the circu- These conditions include older age, hypertension, atheroscle- lation from damaged skeletal muscle. Major causes of rhab- rotic or renovascular disease, and CKD. Patients with hyper- domyolysis include trauma, drugs and toxins, seizures, tension can develop normotensive ischemic ATN if their blood metabolic and electrolyte disorders, endocrinopathies (dia- pressure is decreased to a value lower than what they are betic ketoacidosis, hyperglycemic hyperosmolar syndrome, accustomed to but within normal range. Management involves hypothyroidism), and intense exercise, particularly in treating any volume deficits and decreasing antihypertensive poorly conditioned individuals. Rhabdomyolysis-induced medications to allow the blood pressure to increase to baseline AKI is more likely to occur with serum creatine kinase lev- levels. els >5000 U/L. In addition to elevated serum creatine kinase and serum creatinine levels, hyperkalemia, hypocalcemia, Drug-Induced Acute Tubular Necrosis hyperphosphatemia, hyperuricemia, metabolic acidosis, Drug-induced ATN can be a consequence of prolonged hemo- increased lactate dehydrogenase (LDH) concentration, and dynamic alterations or direct tubular injury (see Table 26). The increased aspartate and alanine aminotransferase levels can drugs associated with prerenal AKI can cause ATN from pro- occur. Urinary findings include FEy, <1% (due to renal vaso- longed hypoperfusion. Early recognition and prompt discon- constriction), myoglobinuria, and pigmented (red) granular tinuation of the drug are essential for renal recovery. The risk casts. of drug-induced ATN increases in older persons and in patients In addition to correcting the underlying cause, preven- with decreased effective arterial circulation, CKD, or concomi- tion and management of AKI involve aggressive intrave- tant nephrotoxin exposure. Hypomagnesemia, hypokalemia, nous isotonic fluid resuscitation aimed at maintaining hypophosphatemia, hypocalcemia, and metabolic acidosis urine output >200 to 300 mL/h. Although limited studies may reflect underlying tubular injury. suggest that alkalinization of the urine with intravenous Osmotic nephrosis is a form of tubular injury due to bicarbonate to increase the urine pH >6.5 may prevent hyperosmolar substances such as sucrose-containing intrave- tubular cast formation, there is no evidence that such alka- nous immunoglobulin, mannitol, hydroxyethyl starch, dex- line diuresis either prevents rhabdomyolysis-related AKI or tran, and contrast media. It is characterized by vacuolization hastens its recovery. If urine alkalinization is used, it should
of drug-induced ATN increases in older persons and in patients In addition to correcting the underlying cause, preven- with decreased effective arterial circulation, CKD, or concomi- tion and management of AKI involve aggressive intrave- tant nephrotoxin exposure. Hypomagnesemia, hypokalemia, nous isotonic fluid resuscitation aimed at maintaining hypophosphatemia, hypocalcemia, and metabolic acidosis urine output >200 to 300 mL/h. Although limited studies may reflect underlying tubular injury. suggest that alkalinization of the urine with intravenous Osmotic nephrosis is a form of tubular injury due to bicarbonate to increase the urine pH >6.5 may prevent hyperosmolar substances such as sucrose-containing intrave- tubular cast formation, there is no evidence that such alka- nous immunoglobulin, mannitol, hydroxyethyl starch, dex- line diuresis either prevents rhabdomyolysis-related AKI or tran, and contrast media. It is characterized by vacuolization hastens its recovery. If urine alkalinization is used, it should 64
Acute Kidney Injury be closely monitored and discontinued if the patient devel- checkpoint inhibitors, and pemetrexed, are an underrecog- ops symptomatic hypocalcemia or arterial pH >7.5, or if nized cause of AIN. urine pH does not increase to >6.5 after several hours. Renal recovery from drug-induced AIN is usually com- Dialysis may be necessary for severe electrolyte and acid- plete if the drug is stopped immediately after the onset of base abnormalities. Most patients have partial or complete kidney injury but may take weeks to several months. renal recovery. Irreversible interstitial fibrosis (chronic tubulointerstitial Heme pigment nephropathy is less common and occurs nephritis) can develop after 2 weeks of continued exposure. when large amounts of heme pigment are released into circula- Kidney biopsy should be considered if there is no improve- tion due to intravascular hemolysis. Causes include glucose- ment in kidney function after 5 to 7 days of drug discontinua- 6-phosphate dehydrogenase (G6PD) deficiency, drug reactions, tion. Early glucocorticoid administration may limit damage cardiopulmonary bypass circuits, incompatible blood transfu- associated with drug-induced AIN. sion, paroxysmal nocturnal hemoglobinuria, malaria, certain poisonings, and snakebites. In addition to elevated serum creati- ¢ Urine eosinophils are neither sensitive nor specific in nine concentration, other laboratory abnormalities include ane- the diagnosis of acute interstitial nephritis, and testing mia, increased LDH, and decreased haptoglobin. Urinary findings should not be obtained. include FEy, <1%, hemoglobinuria, and pigmented granular casts. Treatment of hemoglobinuria involves treating the under- e Drug-induced acute interstitial nephritis is associated lying cause as well as volume repletion with intravenous fluids. with a gradual increase in serum creatinine 7 to 10 days after drug exposure; renal recovery is usually complete if the drug is stopped immediately after the onset of e Acute tubular necrosis due to ischemia, nephrotoxins, kidney injury. and/or sepsis is the most common cause of acute kid- ney injury in hospitalized patients; a history of sepsis, Acute Glomerulonephritis documented protracted hypotension, or nephrotoxin Acute glomerulonephritis with AKI results from immune- exposure along with hemodynamic and volume status mediated damage to glomeruli. Urinary findings include pro- assessment can aid in the diagnosis. teinuria, dysmorphic erythrocytes, and erythrocyte casts (see Table 29; see Figure 2). Constitutional signs and symptoms are Acute Interstitial Nephritis often present. Serologic assays and kidney biopsy identify most Acute interstitial nephritis (AIN) is a common cause of AKI causes. Early recognition is extremely important because, with- and is characterized by inflammation and edema of the inter- out treatment, it can be fatal and result in irreversible kidney stitium. The classic clinical presentation of fever, rash, and damage. See Glomerular Diseases for more information. peripheral eosinophilia occurs in only 10% to 30% of patients with AIN. Urinary findings can include leukocytes, erythro- Acute Vascular Syndromes cytes, and leukocyte casts (see Table 29; see Figure 2). Urine Macrovascular (large and medium vessel) or microvascular eosinophils are neither sensitive nor specific for AIN, and test- (small vessel) disease can cause AKI (see Table 27). ing is no longer recommended for diagnosis. Acute renal arterial occlusion, most often embolic due to Drug-induced AIN, especially due to antibiotics, proton atrial fibrillation or atherosclerotic aortic disease, and acute pump inhibitors, or NSAIDS, is the most common cause of AIN renal vein thrombosis can cause acute renal infarction and and should be considered in any patient with AKI, a character- present as abdominal or flank pain, elevated serum LDH lev- istic urinalysis, and history of any drug exposure (see Table 19). els, and hematuria. A notable risk of renal vein thrombosis Other causes include infections, toxin exposure, and systemic accompanies the nephrotic syndrome, particularly with mem- diseases such as autoimmune disorders (see Table 20). branous nephropathy. Diagnosis may be made by kidney Typically, the serum creatinine gradually increases 7 to 10 days ultrasonography with Doppler. Treatment usually consists of after drug exposure but can increase much sooner following anticoagulation and supportive care. repeat exposure of the drug. Patients with atherosclerotic disease who undergo an Drug-induced AIN from NSAIDs, including selective invasive vascular procedure such as vascular surgery or angiog- cyclooxygenase-2 inhibitors, is usually not associated with raphy are at increased risk for atheroembolic-induced AKI fever, rash, or eosinophilia and develops 6 to 12 months after (cholesterol emboli). Atheroembolic events can occur sponta- drug exposure. AIN from NSAIDs can be associated with the neously or several days to weeks after manipulation of the nephrotic syndrome due to minimal change glomerulopathy aorta. Plaque rupture causes cholesterol embolization to distal or membranous nephropathy. The onset of proton pump small- and medium-sized arteries, resulting in ischemia with inhibitor-induced AIN is variable but typically occurs 10 to end-organ damage. In addition to the kidneys, atheroemboli 13 weeks after exposure. Proton pump inhibitors are thought can affect the arteries in the skin, muscle, gastrointestinal tract, to be a risk factor for the development of CKD. liver, eyes, and central nervous system. Physical examination Chemotherapeutic agents, including ifosfamide, immune findings may include livedo reticularis (lacy network of bluish
be closely monitored and discontinued if the patient devel- checkpoint inhibitors, and pemetrexed, are an underrecog- ops symptomatic hypocalcemia or arterial pH >7.5, or if nized cause of AIN. urine pH does not increase to >6.5 after several hours. Renal recovery from drug-induced AIN is usually com- Dialysis may be necessary for severe electrolyte and acid- plete if the drug is stopped immediately after the onset of base abnormalities. Most patients have partial or complete kidney injury but may take weeks to several months. renal recovery. Irreversible interstitial fibrosis (chronic tubulointerstitial Heme pigment nephropathy is less common and occurs nephritis) can develop after 2 weeks of continued exposure. when large amounts of heme pigment are released into circula- Kidney biopsy should be considered if there is no improve- tion due to intravascular hemolysis. Causes include glucose- ment in kidney function after 5 to 7 days of drug discontinua- 6-phosphate dehydrogenase (G6PD) deficiency, drug reactions, tion. Early glucocorticoid administration may limit damage cardiopulmonary bypass circuits, incompatible blood transfu- associated with drug-induced AIN. sion, paroxysmal nocturnal hemoglobinuria, malaria, certain poisonings, and snakebites. In addition to elevated serum creati- ¢ Urine eosinophils are neither sensitive nor specific in nine concentration, other laboratory abnormalities include ane- the diagnosis of acute interstitial nephritis, and testing mia, increased LDH, and decreased haptoglobin. Urinary findings should not be obtained. include FEy, <1%, hemoglobinuria, and pigmented granular casts. Treatment of hemoglobinuria involves treating the under- e Drug-induced acute interstitial nephritis is associated lying cause as well as volume repletion with intravenous fluids. with a gradual increase in serum creatinine 7 to 10 days after drug exposure; renal recovery is usually complete if the drug is stopped immediately after the onset of e Acute tubular necrosis due to ischemia, nephrotoxins, kidney injury. and/or sepsis is the most common cause of acute kid- ney injury in hospitalized patients; a history of sepsis, Acute Glomerulonephritis documented protracted hypotension, or nephrotoxin Acute glomerulonephritis with AKI results from immune- exposure along with hemodynamic and volume status mediated damage to glomeruli. Urinary findings include pro- assessment can aid in the diagnosis. teinuria, dysmorphic erythrocytes, and erythrocyte casts (see Table 29; see Figure 2). Constitutional signs and symptoms are Acute Interstitial Nephritis often present. Serologic assays and kidney biopsy identify most Acute interstitial nephritis (AIN) is a common cause of AKI causes. Early recognition is extremely important because, with- and is characterized by inflammation and edema of the inter- out treatment, it can be fatal and result in irreversible kidney stitium. The classic clinical presentation of fever, rash, and damage. See Glomerular Diseases for more information. peripheral eosinophilia occurs in only 10% to 30% of patients with AIN. Urinary findings can include leukocytes, erythro- Acute Vascular Syndromes cytes, and leukocyte casts (see Table 29; see Figure 2). Urine Macrovascular (large and medium vessel) or microvascular eosinophils are neither sensitive nor specific for AIN, and test- (small vessel) disease can cause AKI (see Table 27). ing is no longer recommended for diagnosis. Acute renal arterial occlusion, most often embolic due to Drug-induced AIN, especially due to antibiotics, proton atrial fibrillation or atherosclerotic aortic disease, and acute pump inhibitors, or NSAIDS, is the most common cause of AIN renal vein thrombosis can cause acute renal infarction and and should be considered in any patient with AKI, a character- present as abdominal or flank pain, elevated serum LDH lev- istic urinalysis, and history of any drug exposure (see Table 19). els, and hematuria. A notable risk of renal vein thrombosis Other causes include infections, toxin exposure, and systemic accompanies the nephrotic syndrome, particularly with mem- diseases such as autoimmune disorders (see Table 20). branous nephropathy. Diagnosis may be made by kidney Typically, the serum creatinine gradually increases 7 to 10 days ultrasonography with Doppler. Treatment usually consists of after drug exposure but can increase much sooner following anticoagulation and supportive care. repeat exposure of the drug. Patients with atherosclerotic disease who undergo an Drug-induced AIN from NSAIDs, including selective invasive vascular procedure such as vascular surgery or angiog- cyclooxygenase-2 inhibitors, is usually not associated with raphy are at increased risk for atheroembolic-induced AKI fever, rash, or eosinophilia and develops 6 to 12 months after (cholesterol emboli). Atheroembolic events can occur sponta- drug exposure. AIN from NSAIDs can be associated with the neously or several days to weeks after manipulation of the nephrotic syndrome due to minimal change glomerulopathy aorta. Plaque rupture causes cholesterol embolization to distal or membranous nephropathy. The onset of proton pump small- and medium-sized arteries, resulting in ischemia with inhibitor-induced AIN is variable but typically occurs 10 to end-organ damage. In addition to the kidneys, atheroemboli 13 weeks after exposure. Proton pump inhibitors are thought can affect the arteries in the skin, muscle, gastrointestinal tract, to be a risk factor for the development of CKD. liver, eyes, and central nervous system. Physical examination Chemotherapeutic agents, including ifosfamide, immune findings may include livedo reticularis (lacy network of bluish 65
Acute Kidney Injury AKI can also occur from polyarteritis nodosa. It causes microaneurysms of medium size and occasionally small arter- ies that subsequently rupture, resulting in hemorrhage, thrombosis, and organ ischemia and infarction, including AKI. See MKSAP 19 Rheumatology for more information. AKI from microvascular disease can present as throm- botic microangiopathy (TMA) with microangiopathic hemo- lytic anemia, thrombocytopenia, and glomerular capillary thrombosis (see Table 27). See MKSAP 19 Hematology for more information. Urine may show hematuria, erythrocyte casts, and/or proteinuria. Treatment of TMA is based on the underly- ing cause.
AKI can also occur from polyarteritis nodosa. It causes microaneurysms of medium size and occasionally small arter- ies that subsequently rupture, resulting in hemorrhage, thrombosis, and organ ischemia and infarction, including AKI. See MKSAP 19 Rheumatology for more information. AKI from microvascular disease can present as throm- botic microangiopathy (TMA) with microangiopathic hemo- lytic anemia, thrombocytopenia, and glomerular capillary thrombosis (see Table 27). See MKSAP 19 Hematology for more information. Urine may show hematuria, erythrocyte casts, and/or proteinuria. Treatment of TMA is based on the underly- ing cause. e In atheroemboli-induced acute kidney injury (AKI), plaque rupture, especially following a vascular proce- dure, causes cholesterol embolization resulting in ischemia with AKI and multisystem involvement; treat- ment is supportive. FIGURE 19. AHollenhorst plaque is a golden-yellow intra-arterial refractile e Physical findings of atheroembolic disease include livedo body characteristic of cholesterol emboli. This finding is suggestive of artery-to- reticularis, digital gangrene, and yellow refractile bodies artery embolization and may have originated from an ulcerative atherosclerotic plaque located in the internal carotid artery. (Hollenhorst plaques) on funduscopic examination.
e In atheroemboli-induced acute kidney injury (AKI), plaque rupture, especially following a vascular proce- dure, causes cholesterol embolization resulting in ischemia with AKI and multisystem involvement; treat- ment is supportive. FIGURE 19. AHollenhorst plaque is a golden-yellow intra-arterial refractile e Physical findings of atheroembolic disease include livedo body characteristic of cholesterol emboli. This finding is suggestive of artery-to- reticularis, digital gangrene, and yellow refractile bodies artery embolization and may have originated from an ulcerative atherosclerotic plaque located in the internal carotid artery. (Hollenhorst plaques) on funduscopic examination. e Acute kidney injury from thrombotic microangiopathy red vessels, usually seen on legs) (see MKSAP 19 Rheumatology), (TMA) occurs in thrombotic thrombocytopenic pur- Hollenhorst plaques on funduscopic examination (yellow pura, hemolytic uremic syndrome, preeclampsia, the refractile body within arteriole) (Figure 19), ulcerations, and HELLP (Hemolysis, Elevated Liver enzymes, and Low blue toes from ischemia (Figure 20). Laboratory findings can Platelets) syndrome, hypertensive emergency, sclero- include low serum complements, peripheral eosinophilia, and derma renal crisis, and complement-mediated TMA eosinophiluria; urinalysis may be unremarkable or can have (atypical hemolytic uremic syndrome). proteinuria, microscopic hematuria, or erythrocyte casts.
refractile body within arteriole) (Figure 19), ulcerations, and HELLP (Hemolysis, Elevated Liver enzymes, and Low blue toes from ischemia (Figure 20). Laboratory findings can Platelets) syndrome, hypertensive emergency, sclero- include low serum complements, peripheral eosinophilia, and derma renal crisis, and complement-mediated TMA eosinophiluria; urinalysis may be unremarkable or can have (atypical hemolytic uremic syndrome). proteinuria, microscopic hematuria, or erythrocyte casts. Treatment of atheroemboli is supportive and consists of risk Intratubular Obstruction factor reduction with aspirin, statins, and management of Intratubular obstruction can cause AKI through precipitation hypertension. Renal prognosis is poor. of either protein or crystals within the tubular lumen. Examples include monoclonal light chain deposition in multi- ple myeloma, calcium oxalate deposition from ethylene glycol
Treatment of atheroemboli is supportive and consists of risk Intratubular Obstruction factor reduction with aspirin, statins, and management of Intratubular obstruction can cause AKI through precipitation hypertension. Renal prognosis is poor. of either protein or crystals within the tubular lumen. Examples include monoclonal light chain deposition in multi- ple myeloma, calcium oxalate deposition from ethylene glycol ingestion, crystals from drugs, and uric acid from tumor lysis syndrome (see Table 27). In multiple myeloma, AKI from light chain cast nephrop- athy is the most common type of kidney disease. Cast nephrop- athy is due to direct tubular toxicity and obstruction from the precipitation of filtered free light chains. See Kidney Manifestations of Deposition Diseases for more information. Ethylene glycol intoxication causes AKI from intratubular precipitation of calcium oxalate crystals, which can be seen on urine microscopy. Ethylene glycol should be suspected in a patient with a history of ingestion and whose laboratory studies demonstrate an increased anion gap metabolic acidosis and osmolal gap. Treatment consists of supportive care, the alcohol dehydrogenase inhibitor fomepizole, and hemodialysis if needed. Orlistat, a gastrointestinal lipase inhibitor used to induce clini- cally significant weight loss by fat malabsorption, has also been associated with intratubular calcium oxalate deposition and AKI.
ingestion, crystals from drugs, and uric acid from tumor lysis syndrome (see Table 27). In multiple myeloma, AKI from light chain cast nephrop- athy is the most common type of kidney disease. Cast nephrop- athy is due to direct tubular toxicity and obstruction from the precipitation of filtered free light chains. See Kidney Manifestations of Deposition Diseases for more information. Ethylene glycol intoxication causes AKI from intratubular precipitation of calcium oxalate crystals, which can be seen on urine microscopy. Ethylene glycol should be suspected in a patient with a history of ingestion and whose laboratory studies demonstrate an increased anion gap metabolic acidosis and osmolal gap. Treatment consists of supportive care, the alcohol dehydrogenase inhibitor fomepizole, and hemodialysis if needed. Orlistat, a gastrointestinal lipase inhibitor used to induce clini- cally significant weight loss by fat malabsorption, has also been associated with intratubular calcium oxalate deposition and AKI. FIGURE 20. Blue toe syndrome. Cholesterol emboli causing necrosis of the skin High doses of vitamin C, which is metabolized to oxalate, can also on the toes. lead to AKI from calcium oxalate precipitation in the tubules.
ingestion, crystals from drugs, and uric acid from tumor lysis syndrome (see Table 27). In multiple myeloma, AKI from light chain cast nephrop- athy is the most common type of kidney disease. Cast nephrop- athy is due to direct tubular toxicity and obstruction from the precipitation of filtered free light chains. See Kidney Manifestations of Deposition Diseases for more information. Ethylene glycol intoxication causes AKI from intratubular precipitation of calcium oxalate crystals, which can be seen on urine microscopy. Ethylene glycol should be suspected in a patient with a history of ingestion and whose laboratory studies demonstrate an increased anion gap metabolic acidosis and osmolal gap. Treatment consists of supportive care, the alcohol dehydrogenase inhibitor fomepizole, and hemodialysis if needed. Orlistat, a gastrointestinal lipase inhibitor used to induce clini- cally significant weight loss by fat malabsorption, has also been associated with intratubular calcium oxalate deposition and AKI. FIGURE 20. Blue toe syndrome. Cholesterol emboli causing necrosis of the skin High doses of vitamin C, which is metabolized to oxalate, can also on the toes. lead to AKI from calcium oxalate precipitation in the tubules. 66
Acute Kidney Injury Drugs associated with crystal-induced AKI are listed in and incomplete voiding. Acute nephrolithiasis may present Table 26. Urinary findings include hematuria, pyuria, and with flank pain and hematuria. Presenting signs of obstructive crystals. AKI is usually reversed after discontinuation of the nephropathy may include hypertension. A distended palpable drug. Predisposing factors include volume depletion, CKD, bladder may be evident in bladder outlet obstruction. Serum and changes in urine pH. Correction of volume depletion with creatinine is typically elevated at presentation and is some- intravenous fluids is critical for both the prevention and treat- times asymptomatic. Hyperkalemia and features of distal renal ment of crystal-induced AKI. High-dose intravenous acyclovir tubular acidosis may also be evident. can cause acyclovir crystal deposition in the tubules, which Lower urinary tract obstruction can be diagnosed by an can be prevented by prior intravenous fluid administration elevated post-void bladder residual volume on ultrasound. and slow rate of drug infusion. Because crystals from sulfona- Hydronephrosis on kidney ultrasound is present in most mide antibiotics and methotrexate are more likely to form in causes of obstruction, but false-negative results may occur in acidic urine, urinary alkalinization can prevent crystal deposi- the early stages or from encasement of the ureter or kidney, as tion. Crystals from protease inhibitors can cause AKI from seen in retroperitoneal disease. Noncontrast CT is indicated for both crystal deposition and nephrolithiasis. suspected nephrolithiasis. Although less sensitive than CT, Acute phosphate nephropathy is a potentially irreversible kidney ultrasonography is less expensive, has no radiation cause of AKI due to phosphate-containing bowel preparations. exposure, and can be used in pregnant women or when CT is Although many of these agents have been removed from the unavailable. Treatment focuses on reversing the cause of the U.S. market, acute phosphate nephropathy is occasionally seen obstruction. Renal prognosis depends upon the severity and in patients, particularly those with preexisting CKD, who have duration of the obstruction. Renal recovery is generally good if taken sodium phosphate retention enemas. A transient severe the obstruction is relieved within 1 to 2 weeks. increase in serum phosphate in the setting of volume deple- tion causes acute and chronic tubular injury from tubular and e Postrenal acute kidney injury can occur from obstruction interstitial precipitation of calcium phosphate crystals. AKI anywhere from the renal pelvis to the external urethral can present days to months after exposure. Predisposing fac- tors include volume depletion, CKD, older age, NSAID use, and meatus; diagnosis can be made via ultrasonography or noncontrast CT, with generally good renal recovery if the hypertension treated with ACE inhibitors, angiotensin recep- tor blockers, or diuretics. obstruction is relieved within 1 to 2 weeks.
Drugs associated with crystal-induced AKI are listed in and incomplete voiding. Acute nephrolithiasis may present Table 26. Urinary findings include hematuria, pyuria, and with flank pain and hematuria. Presenting signs of obstructive crystals. AKI is usually reversed after discontinuation of the nephropathy may include hypertension. A distended palpable drug. Predisposing factors include volume depletion, CKD, bladder may be evident in bladder outlet obstruction. Serum and changes in urine pH. Correction of volume depletion with creatinine is typically elevated at presentation and is some- intravenous fluids is critical for both the prevention and treat- times asymptomatic. Hyperkalemia and features of distal renal ment of crystal-induced AKI. High-dose intravenous acyclovir tubular acidosis may also be evident. can cause acyclovir crystal deposition in the tubules, which Lower urinary tract obstruction can be diagnosed by an can be prevented by prior intravenous fluid administration elevated post-void bladder residual volume on ultrasound. and slow rate of drug infusion. Because crystals from sulfona- Hydronephrosis on kidney ultrasound is present in most mide antibiotics and methotrexate are more likely to form in causes of obstruction, but false-negative results may occur in acidic urine, urinary alkalinization can prevent crystal deposi- the early stages or from encasement of the ureter or kidney, as tion. Crystals from protease inhibitors can cause AKI from seen in retroperitoneal disease. Noncontrast CT is indicated for both crystal deposition and nephrolithiasis. suspected nephrolithiasis. Although less sensitive than CT, Acute phosphate nephropathy is a potentially irreversible kidney ultrasonography is less expensive, has no radiation cause of AKI due to phosphate-containing bowel preparations. exposure, and can be used in pregnant women or when CT is Although many of these agents have been removed from the unavailable. Treatment focuses on reversing the cause of the U.S. market, acute phosphate nephropathy is occasionally seen obstruction. Renal prognosis depends upon the severity and in patients, particularly those with preexisting CKD, who have duration of the obstruction. Renal recovery is generally good if taken sodium phosphate retention enemas. A transient severe the obstruction is relieved within 1 to 2 weeks. increase in serum phosphate in the setting of volume deple- tion causes acute and chronic tubular injury from tubular and e Postrenal acute kidney injury can occur from obstruction interstitial precipitation of calcium phosphate crystals. AKI anywhere from the renal pelvis to the external urethral can present days to months after exposure. Predisposing fac- tors include volume depletion, CKD, older age, NSAID use, and meatus; diagnosis can be made via ultrasonography or noncontrast CT, with generally good renal recovery if the hypertension treated with ACE inhibitors, angiotensin recep- tor blockers, or diuretics. obstruction is relieved within 1 to 2 weeks. e In patients with postrenal acute kidney injury, the pres- ence of normal urine output or polyuria do not exclude the possibility of obstructive uropathy. ¢ Intratubular obstruction causes of acute kidney injury include monoclonal light chain deposition in multiple myeloma; calcium oxalate deposition from ethylene gly- col ingestion, orlistat, and high doses of vitamin C; crys- Specific Clinical Settings tals from drugs; and uric acid or calcium phosphate Contrast-Associated Nephropathy crystal deposition from tumor lysis syndrome. Contrast-associated nephropathy (CAN), defined as an
e In patients with postrenal acute kidney injury, the pres- ence of normal urine output or polyuria do not exclude the possibility of obstructive uropathy. ¢ Intratubular obstruction causes of acute kidney injury include monoclonal light chain deposition in multiple myeloma; calcium oxalate deposition from ethylene gly- col ingestion, orlistat, and high doses of vitamin C; crys- Specific Clinical Settings tals from drugs; and uric acid or calcium phosphate Contrast-Associated Nephropathy crystal deposition from tumor lysis syndrome. Contrast-associated nephropathy (CAN), defined as an increase in serum creatinine levels within 24 to 48 hours of Postrenal Disease contrast exposure, is a common cause of reversible AKI in the Postrenal AKI can occur from obstruction anywhere from the hospital setting. Contrast-induced nephropathy (CIN) includes renal pelvis to the external urethral meatus (see Table 27). that subset of CAN in which the kidney injury can be more Upper urinary tract obstruction (at the level of the ureters or definitively linked to the contrast. Multiple risk factors have renal pelvis) must be bilateral or affect a single functioning been associated with CAN, but a baseline reduction in esti- kidney to cause AKI. Obstruction of urinary flow leads to mated GFR (eGFR) appears most important, especially in hydronephrosis and eventual renal parenchymal damage. If patients with AKI as well as in patients with CKD and an eGFR postrenal AKI is not treated promptly, the obstruction can <30 mL/min/1.73 m2. predispose the patient to urinary tract infections and urosep- The AKI tends to be nonoliguric, with an FEy, <1%. The sis, and it can also lead to CKD and ESKD. urine sediment may be bland or show classic ATN findings. In Postrenal AKI should be suspected in patients with a addition to advanced CKD, risk factors include diabetic kidney history of benign prostatic hyperplasia, diabetes, nephro- disease, conditions of decreased renal perfusion, high contrast lithiasis, pelvic malignancies, previous retroperitoneal radia- dose, hyperosmolar contrast, and intra-arterial contrast tion therapy, abdominal or pelvic surgeries, or retroperitoneal administration. The risk for CAN is lower than previously adenopathy. Patients can present with anuria, oliguria, poly- thought. Use of contrast without a suitable alternative should uria, or normal urine output. Symptoms of lower tract not be avoided solely on the basis of CAN risk. obstruction include abdominal fullness or pain, urinary fre- Preventive strategies for patients at high risk for quency, urgency, hesitancy, nocturia, overflow incontinence, CAN include minimizing the amount of contrast and
increase in serum creatinine levels within 24 to 48 hours of Postrenal Disease contrast exposure, is a common cause of reversible AKI in the Postrenal AKI can occur from obstruction anywhere from the hospital setting. Contrast-induced nephropathy (CIN) includes renal pelvis to the external urethral meatus (see Table 27). that subset of CAN in which the kidney injury can be more Upper urinary tract obstruction (at the level of the ureters or definitively linked to the contrast. Multiple risk factors have renal pelvis) must be bilateral or affect a single functioning been associated with CAN, but a baseline reduction in esti- kidney to cause AKI. Obstruction of urinary flow leads to mated GFR (eGFR) appears most important, especially in hydronephrosis and eventual renal parenchymal damage. If patients with AKI as well as in patients with CKD and an eGFR postrenal AKI is not treated promptly, the obstruction can <30 mL/min/1.73 m2. predispose the patient to urinary tract infections and urosep- The AKI tends to be nonoliguric, with an FEy, <1%. The sis, and it can also lead to CKD and ESKD. urine sediment may be bland or show classic ATN findings. In Postrenal AKI should be suspected in patients with a addition to advanced CKD, risk factors include diabetic kidney history of benign prostatic hyperplasia, diabetes, nephro- disease, conditions of decreased renal perfusion, high contrast lithiasis, pelvic malignancies, previous retroperitoneal radia- dose, hyperosmolar contrast, and intra-arterial contrast tion therapy, abdominal or pelvic surgeries, or retroperitoneal administration. The risk for CAN is lower than previously adenopathy. Patients can present with anuria, oliguria, poly- thought. Use of contrast without a suitable alternative should uria, or normal urine output. Symptoms of lower tract not be avoided solely on the basis of CAN risk. obstruction include abdominal fullness or pain, urinary fre- Preventive strategies for patients at high risk for quency, urgency, hesitancy, nocturia, overflow incontinence, CAN include minimizing the amount of contrast and 67
Acute Kidney Injury prophylactically administering intravenous isotonic saline. Therapeutic interventions include treatment with vasocon- Prophylactic saline should be administered to all patients with strictors such as midodrine, octreotide, terlipressin (although an eGFR <30 mL/min/1.73 m? and should be considered for not available in the United States or Canada), or norepineph- patients with an eGFR of 30 to 44 mL/min/1.73 m? who have rine, in combination with albumin infusion. Additional inter- other risk factors for AKI. There is no role for prophylactic ventions may include placement of a transjugular intrahepatic intravenous sodium bicarbonate nor hemodialysis or hemofil- portosystemic shunt in select patients, renal replacement tration following contrast exposure. Treatment of CAN is therapy, and liver transplantation. Renal replacement therapy supportive. is usually reserved for patients with severe AKI who are liver transplant candidates.
prophylactically administering intravenous isotonic saline. Therapeutic interventions include treatment with vasocon- Prophylactic saline should be administered to all patients with strictors such as midodrine, octreotide, terlipressin (although an eGFR <30 mL/min/1.73 m? and should be considered for not available in the United States or Canada), or norepineph- patients with an eGFR of 30 to 44 mL/min/1.73 m? who have rine, in combination with albumin infusion. Additional inter- other risk factors for AKI. There is no role for prophylactic ventions may include placement of a transjugular intrahepatic intravenous sodium bicarbonate nor hemodialysis or hemofil- portosystemic shunt in select patients, renal replacement tration following contrast exposure. Treatment of CAN is therapy, and liver transplantation. Renal replacement therapy supportive. is usually reserved for patients with severe AKI who are liver transplant candidates. Cardiorenal Syndrome Cardiorenal syndrome (CRS) is a disorder of the heart and Tumor Lysis Syndrome kidneys whereby acute or long-term dysfunction in one organ Tumor lysis syndrome (TLS) is characterized by the rapid lysis induces acute or long-term dysfunction in the other. CRS is of malignant cells leading to hyperuricemia, hyperkalemia, characterized by the triad of concomitant decreased kidney hyperphosphatemia, hypocalcemia, and AKI. TLS typically function, diuretic-resistant heart failure with congestion, and occurs after initiation of chemotherapy in hematologic malig- worsening kidney function during heart failure therapy. It is nancies with high cell turnover rate, rapid growth rate, or high seen primarily in heart failure with reduced ejection fraction. tumor bulk (acute leukemia or Burkitt lymphoma); however, The decreased kidney function in CRS is thought to be due to it can also occur independent of chemotherapy. AKI occurs neurohumoral activation, venous congestion and increased from deposition of uric acid and/or calcium phosphate crystals renal venous pressure, reduced renal perfusion, and right ven- in the renal tubules. tricular dysfunction. Management of TLS requires the initiation of preventive Management is challenging because treatment directed measures in high-risk patients before cytotoxic therapy, as toward improving cardiac function (diuretics, ACE inhibitor/ well as the timely initiation of supportive care for patients angiotensin receptor blocker, vasodilators, and inotropes) can who develop TLS. Treatment of established TLS includes worsen kidney function. Current evidence does not support intravenous volume expansion, urate-lowering therapy, the use of ultrafiltration over intensive diuretic management. management of hyperkalemia and hyperphosphatemia, and Decreased kidney function in patients with heart failure is an renal replacement therapy in refractory cases. Patients at risk independent risk factor for all-cause mortality. for or presenting with TLS require aggressive volume expan-
Cardiorenal Syndrome Cardiorenal syndrome (CRS) is a disorder of the heart and Tumor Lysis Syndrome kidneys whereby acute or long-term dysfunction in one organ Tumor lysis syndrome (TLS) is characterized by the rapid lysis induces acute or long-term dysfunction in the other. CRS is of malignant cells leading to hyperuricemia, hyperkalemia, characterized by the triad of concomitant decreased kidney hyperphosphatemia, hypocalcemia, and AKI. TLS typically function, diuretic-resistant heart failure with congestion, and occurs after initiation of chemotherapy in hematologic malig- worsening kidney function during heart failure therapy. It is nancies with high cell turnover rate, rapid growth rate, or high seen primarily in heart failure with reduced ejection fraction. tumor bulk (acute leukemia or Burkitt lymphoma); however, The decreased kidney function in CRS is thought to be due to it can also occur independent of chemotherapy. AKI occurs neurohumoral activation, venous congestion and increased from deposition of uric acid and/or calcium phosphate crystals renal venous pressure, reduced renal perfusion, and right ven- in the renal tubules. tricular dysfunction. Management of TLS requires the initiation of preventive Management is challenging because treatment directed measures in high-risk patients before cytotoxic therapy, as toward improving cardiac function (diuretics, ACE inhibitor/ well as the timely initiation of supportive care for patients angiotensin receptor blocker, vasodilators, and inotropes) can who develop TLS. Treatment of established TLS includes worsen kidney function. Current evidence does not support intravenous volume expansion, urate-lowering therapy, the use of ultrafiltration over intensive diuretic management. management of hyperkalemia and hyperphosphatemia, and Decreased kidney function in patients with heart failure is an renal replacement therapy in refractory cases. Patients at risk independent risk factor for all-cause mortality. for or presenting with TLS require aggressive volume expan- sion to achieve a urine output of at least 80 to 100 mL/kg/h. Urinary alkalinization is no longer recommended because Hepatorenal Syndrome the high urine pH can cause an increase in calcium phos- Hepatorenal syndrome (HRS) is a potentially reversible func- phate crystal deposition. Allopurinol or febuxostat, inhibitors tional kidney impairment that occurs in the setting of portal of xanthine oxidase, prevent the formation of new uric acid hypertension due to liver cirrhosis, severe alcoholic hepatitis, and are recommended as prophylaxis for patients at interme- or acute liver failure. HRS is characterized by increased renal diate risk for TLS (those with highly chemotherapy-sensitive vasoconstriction and peripheral and splanchnic arterial vaso- solid tumors); it has no effect on existing serum urate levels. dilation. Tubular function is preserved with the absence of Rasburicase, a recombinant urate oxidase that makes uric significant hematuria and proteinuria, as well as lack of renal acid more soluble in urine with rapid reduction in serum histological changes. Urine sodium concentration is typically urate levels, is given to patients at high risk for or with TLS. <10 mEq/L (10 mmol/L). See MKSAP 19 Gastroenterology and Rasburicase is contraindicated in patients with G6PD Hepatology for more information. deficiency. Type 1 HRS is a clinical diagnosis made after exclusion of other causes of kidney dysfunction. It is characterized by a rise in serum creatinine of at least 0.3 mg/dL (26.5 umol/L) and/or Abdominal Compartment Syndrome 250% from baseline within 48 hours, bland urinalysis, and Abdominal compartment syndrome (ACS) is defined as a sus- normal findings on kidney ultrasound. Patients are often olig- tained elevated intra-abdominal pressure (IAP) associated uric. Lack of improvement in kidney function after with- with new organ dysfunction. IAP >20 mm Hg is commonly drawal of diuretics and 2 days of volume expansion with associated with ACS, although the absolute pressure measure- intravenous albumin supports the diagnosis. Type 2 HRS is ment is not a sufficient criterion. ACS occurs in the setting of defined as a more gradual decline in kidney function associ- abdominal surgery, trauma, hemoperitoneum, retroperitoneal ated with refractory ascites. bleed, ascites, bowel obstruction, ileus, and pancreatitis. It can Patients with HRS have an overall poor prognosis without also occur from capillary leak with concurrent massive fluid liver transplantation. General management includes discon- resuscitation. Increasing IAP causes hypoperfusion and tinuing diuretics, restricting sodium, restricting water in ischemia of the intestines and other peritoneal and retroperi- hyponatremic patients, and searching for precipitating factors. toneal structures, leading to hemodynamic, respiratory,
sion to achieve a urine output of at least 80 to 100 mL/kg/h. Urinary alkalinization is no longer recommended because Hepatorenal Syndrome the high urine pH can cause an increase in calcium phos- Hepatorenal syndrome (HRS) is a potentially reversible func- phate crystal deposition. Allopurinol or febuxostat, inhibitors tional kidney impairment that occurs in the setting of portal of xanthine oxidase, prevent the formation of new uric acid hypertension due to liver cirrhosis, severe alcoholic hepatitis, and are recommended as prophylaxis for patients at interme- or acute liver failure. HRS is characterized by increased renal diate risk for TLS (those with highly chemotherapy-sensitive vasoconstriction and peripheral and splanchnic arterial vaso- solid tumors); it has no effect on existing serum urate levels. dilation. Tubular function is preserved with the absence of Rasburicase, a recombinant urate oxidase that makes uric significant hematuria and proteinuria, as well as lack of renal acid more soluble in urine with rapid reduction in serum histological changes. Urine sodium concentration is typically urate levels, is given to patients at high risk for or with TLS. <10 mEq/L (10 mmol/L). See MKSAP 19 Gastroenterology and Rasburicase is contraindicated in patients with G6PD Hepatology for more information. deficiency. Type 1 HRS is a clinical diagnosis made after exclusion of other causes of kidney dysfunction. It is characterized by a rise in serum creatinine of at least 0.3 mg/dL (26.5 umol/L) and/or Abdominal Compartment Syndrome 250% from baseline within 48 hours, bland urinalysis, and Abdominal compartment syndrome (ACS) is defined as a sus- normal findings on kidney ultrasound. Patients are often olig- tained elevated intra-abdominal pressure (IAP) associated uric. Lack of improvement in kidney function after with- with new organ dysfunction. IAP >20 mm Hg is commonly drawal of diuretics and 2 days of volume expansion with associated with ACS, although the absolute pressure measure- intravenous albumin supports the diagnosis. Type 2 HRS is ment is not a sufficient criterion. ACS occurs in the setting of defined as a more gradual decline in kidney function associ- abdominal surgery, trauma, hemoperitoneum, retroperitoneal ated with refractory ascites. bleed, ascites, bowel obstruction, ileus, and pancreatitis. It can Patients with HRS have an overall poor prognosis without also occur from capillary leak with concurrent massive fluid liver transplantation. General management includes discon- resuscitation. Increasing IAP causes hypoperfusion and tinuing diuretics, restricting sodium, restricting water in ischemia of the intestines and other peritoneal and retroperi- hyponatremic patients, and searching for precipitating factors. toneal structures, leading to hemodynamic, respiratory, 68
Acute Kidney Injury neurologic, and kidney impairment. Renal vein compression complications, including hyperkalemia, metabolic acidosis, and renal artery vasoconstriction can cause oliguric AKI. volume overload refractory to diuretics, uremic manifesta- ACS is diagnosed by measuring IAP; measurement of tions, and dialyzable toxins. Options for RRT for AKI include bladder pressure with an indwelling catheter is the standard intermittent hemodialysis (IHD), continuous renal replace- methodology. Management includes supportive therapy, ment therapy (CRRT), “hybrid” therapies such as prolonged abdominal compartment decompression, and correction of intermittent renal replacement therapy (PIRRT), and perito- positive fluid balance. neal dialysis (PD). IHD, CRRT, and PIRRT are extracorporeal therapies that require vascular access in the form of a large- bore, double-lumen central venous catheter; PD requires the e Preventive strategies for patients at high risk for contrast- placement of an intra-abdominal dialysis catheter and is uti- associated nephropathy include minimizing the amount lized less frequently for AKI than for ESKD. of contrast and expanding volume with intravenous iso- IHD, typically delivered 3 to 6 times a week for 3 to 5 hours tonic saline. per session, allows for rapid correction of electrolyte distur- ¢ Cardiorenal syndrome is characterized by the triad of con- bances and rapid removal of drugs or toxins. The main disad- comitant decreased kidney function, diuretic-resistant vantage of IHD is the risk for hypotension caused by the rapid heart failure with congestion, and worsening kidney solute and volume removal. CRRT represents a variety of dialysis function during heart failure therapy. modalities developed specifically to manage critically ill patients
bladder pressure with an indwelling catheter is the standard intermittent hemodialysis (IHD), continuous renal replace- methodology. Management includes supportive therapy, ment therapy (CRRT), “hybrid” therapies such as prolonged abdominal compartment decompression, and correction of intermittent renal replacement therapy (PIRRT), and perito- positive fluid balance. neal dialysis (PD). IHD, CRRT, and PIRRT are extracorporeal therapies that require vascular access in the form of a large- bore, double-lumen central venous catheter; PD requires the e Preventive strategies for patients at high risk for contrast- placement of an intra-abdominal dialysis catheter and is uti- associated nephropathy include minimizing the amount lized less frequently for AKI than for ESKD. of contrast and expanding volume with intravenous iso- IHD, typically delivered 3 to 6 times a week for 3 to 5 hours tonic saline. per session, allows for rapid correction of electrolyte distur- ¢ Cardiorenal syndrome is characterized by the triad of con- bances and rapid removal of drugs or toxins. The main disad- comitant decreased kidney function, diuretic-resistant vantage of IHD is the risk for hypotension caused by the rapid heart failure with congestion, and worsening kidney solute and volume removal. CRRT represents a variety of dialysis function during heart failure therapy. modalities developed specifically to manage critically ill patients ¢ General management of hepatorenal syndrome includes with AKI who cannot tolerate IHD due to hemodynamic insta- discontinuing diuretics, restricting sodium, and treat- bility. CRRT is administered 24 hours daily and removes solutes ment with vasoconstrictors in combination with albumin and fluid much more slowly than IHD, resulting in better hemo-
¢ General management of hepatorenal syndrome includes with AKI who cannot tolerate IHD due to hemodynamic insta- discontinuing diuretics, restricting sodium, and treat- bility. CRRT is administered 24 hours daily and removes solutes ment with vasoconstrictors in combination with albumin and fluid much more slowly than IHD, resulting in better hemo- infusion. dynamic tolerance. PIRRT removes solutes and fluid more slowly than IHD but more quickly than CRRT and is adminis- e Treatment of established tumor lysis syndrome includes tered 8 to 12 hours daily. Acute PD is not as effective as the other intravenous volume expansion, rasburicase, manage- forms of RRT but may be useful when the other types of RRT are ment of hyperkalemia and hyperphosphatemia, and unavailable or vascular access cannot be obtained. renal replacement therapy in refractory cases. Randomized clinical trials have not showna survival ben- e Abdominal compartment syndrome is diagnosed by efit of CRRT over IHD or PIRRT for critically ill AKI patients. measurement of bladder pressure with an indwelling CRRT or PIRRT is chosen for patients who are hemodynami- catheter. cally unstable. CRRT is also preferred in patients with cerebral edema because IHD may worsen neurologic status by compro- mising cerebral perfusion pressure. IHD is favored in patients Management who need rapid solute removal, such as those with severe General Considerations hyperkalemia or drug intoxications. Transitions in therapy are In most cases of AKI, treatment of the underlying medical common depending on the changing needs of the patient. condition and discontinuation of nephrotoxic medications Studies of the timing of RRT initiation in critically ill lead to improvement in kidney function. No specific pharma- patients and those with sepsis demonstrate no mortality ben- cologic therapy is effective in established ATN. Supportive efit to early introduction of RRT compared with based on usual measures include optimizing hemodynamics and renal perfu- clinical criteria. In fact, the latter strategy was sometimes asso- sion, preventing further kidney injury, treating AKI complica- ciated with avoiding the need for RRT. tions, and providing appropriate nutrition. Diuretics can be used for volume overload. Bicarbonate can be administered to e In most cases of acute kidney injury, treatment of the correct metabolic acidosis. Dietary potassium, magnesium, underlying medical condition and discontinuation of and phosphate should be restricted. Phosphate binders may be nephrotoxic medications lead to improvement in kid- required to prevent severe hyperphosphatemia. Medication ney function. dose adjustments for diminished GFR are necessary to avoid toxicities. An episode of AKI increases the risk for new or e Patients with acute kidney injury should be evaluated in
infusion. dynamic tolerance. PIRRT removes solutes and fluid more slowly than IHD but more quickly than CRRT and is adminis- e Treatment of established tumor lysis syndrome includes tered 8 to 12 hours daily. Acute PD is not as effective as the other intravenous volume expansion, rasburicase, manage- forms of RRT but may be useful when the other types of RRT are ment of hyperkalemia and hyperphosphatemia, and unavailable or vascular access cannot be obtained. renal replacement therapy in refractory cases. Randomized clinical trials have not showna survival ben- e Abdominal compartment syndrome is diagnosed by efit of CRRT over IHD or PIRRT for critically ill AKI patients. measurement of bladder pressure with an indwelling CRRT or PIRRT is chosen for patients who are hemodynami- catheter. cally unstable. CRRT is also preferred in patients with cerebral edema because IHD may worsen neurologic status by compro- mising cerebral perfusion pressure. IHD is favored in patients Management who need rapid solute removal, such as those with severe General Considerations hyperkalemia or drug intoxications. Transitions in therapy are In most cases of AKI, treatment of the underlying medical common depending on the changing needs of the patient. condition and discontinuation of nephrotoxic medications Studies of the timing of RRT initiation in critically ill lead to improvement in kidney function. No specific pharma- patients and those with sepsis demonstrate no mortality ben- cologic therapy is effective in established ATN. Supportive efit to early introduction of RRT compared with based on usual measures include optimizing hemodynamics and renal perfu- clinical criteria. In fact, the latter strategy was sometimes asso- sion, preventing further kidney injury, treating AKI complica- ciated with avoiding the need for RRT. tions, and providing appropriate nutrition. Diuretics can be used for volume overload. Bicarbonate can be administered to e In most cases of acute kidney injury, treatment of the correct metabolic acidosis. Dietary potassium, magnesium, underlying medical condition and discontinuation of and phosphate should be restricted. Phosphate binders may be nephrotoxic medications lead to improvement in kid- required to prevent severe hyperphosphatemia. Medication ney function. dose adjustments for diminished GFR are necessary to avoid toxicities. An episode of AKI increases the risk for new or e Patients with acute kidney injury should be evaluated in worsening CKD. Patients with AKI should be monitored dur- follow-up to monitor for complete recovery of function
infusion. dynamic tolerance. PIRRT removes solutes and fluid more slowly than IHD but more quickly than CRRT and is adminis- e Treatment of established tumor lysis syndrome includes tered 8 to 12 hours daily. Acute PD is not as effective as the other intravenous volume expansion, rasburicase, manage- forms of RRT but may be useful when the other types of RRT are ment of hyperkalemia and hyperphosphatemia, and unavailable or vascular access cannot be obtained. renal replacement therapy in refractory cases. Randomized clinical trials have not showna survival ben- e Abdominal compartment syndrome is diagnosed by efit of CRRT over IHD or PIRRT for critically ill AKI patients. measurement of bladder pressure with an indwelling CRRT or PIRRT is chosen for patients who are hemodynami- catheter. cally unstable. CRRT is also preferred in patients with cerebral edema because IHD may worsen neurologic status by compro- mising cerebral perfusion pressure. IHD is favored in patients Management who need rapid solute removal, such as those with severe General Considerations hyperkalemia or drug intoxications. Transitions in therapy are In most cases of AKI, treatment of the underlying medical common depending on the changing needs of the patient. condition and discontinuation of nephrotoxic medications Studies of the timing of RRT initiation in critically ill lead to improvement in kidney function. No specific pharma- patients and those with sepsis demonstrate no mortality ben- cologic therapy is effective in established ATN. Supportive efit to early introduction of RRT compared with based on usual measures include optimizing hemodynamics and renal perfu- clinical criteria. In fact, the latter strategy was sometimes asso- sion, preventing further kidney injury, treating AKI complica- ciated with avoiding the need for RRT. tions, and providing appropriate nutrition. Diuretics can be used for volume overload. Bicarbonate can be administered to e In most cases of acute kidney injury, treatment of the correct metabolic acidosis. Dietary potassium, magnesium, underlying medical condition and discontinuation of and phosphate should be restricted. Phosphate binders may be nephrotoxic medications lead to improvement in kid- required to prevent severe hyperphosphatemia. Medication ney function. dose adjustments for diminished GFR are necessary to avoid toxicities. An episode of AKI increases the risk for new or e Patients with acute kidney injury should be evaluated in worsening CKD. Patients with AKI should be monitored dur- follow-up to monitor for complete recovery of function ing follow-up for complete recovery of function and/or emer- and/or emergence or worsening of chronic kidney disease.
infusion. dynamic tolerance. PIRRT removes solutes and fluid more slowly than IHD but more quickly than CRRT and is adminis- e Treatment of established tumor lysis syndrome includes tered 8 to 12 hours daily. Acute PD is not as effective as the other intravenous volume expansion, rasburicase, manage- forms of RRT but may be useful when the other types of RRT are ment of hyperkalemia and hyperphosphatemia, and unavailable or vascular access cannot be obtained. renal replacement therapy in refractory cases. Randomized clinical trials have not showna survival ben- e Abdominal compartment syndrome is diagnosed by efit of CRRT over IHD or PIRRT for critically ill AKI patients. measurement of bladder pressure with an indwelling CRRT or PIRRT is chosen for patients who are hemodynami- catheter. cally unstable. CRRT is also preferred in patients with cerebral edema because IHD may worsen neurologic status by compro- mising cerebral perfusion pressure. IHD is favored in patients Management who need rapid solute removal, such as those with severe General Considerations hyperkalemia or drug intoxications. Transitions in therapy are In most cases of AKI, treatment of the underlying medical common depending on the changing needs of the patient. condition and discontinuation of nephrotoxic medications Studies of the timing of RRT initiation in critically ill lead to improvement in kidney function. No specific pharma- patients and those with sepsis demonstrate no mortality ben- cologic therapy is effective in established ATN. Supportive efit to early introduction of RRT compared with based on usual measures include optimizing hemodynamics and renal perfu- clinical criteria. In fact, the latter strategy was sometimes asso- sion, preventing further kidney injury, treating AKI complica- ciated with avoiding the need for RRT. tions, and providing appropriate nutrition. Diuretics can be used for volume overload. Bicarbonate can be administered to e In most cases of acute kidney injury, treatment of the correct metabolic acidosis. Dietary potassium, magnesium, underlying medical condition and discontinuation of and phosphate should be restricted. Phosphate binders may be nephrotoxic medications lead to improvement in kid- required to prevent severe hyperphosphatemia. Medication ney function. dose adjustments for diminished GFR are necessary to avoid toxicities. An episode of AKI increases the risk for new or e Patients with acute kidney injury should be evaluated in worsening CKD. Patients with AKI should be monitored dur- follow-up to monitor for complete recovery of function ing follow-up for complete recovery of function and/or emer- and/or emergence or worsening of chronic kidney disease. gence of CKD, and patients who had preexisting CKD should ¢ Renal replacement therapy is used to manage the urgent be evaluated for worsening function. complications of severe acute kidney injury, including hyperkalemia, metabolic acidosis, volume overload refractory to diuretics, uremic manifestations, and dia- Renal Replacement Therapy lyzable toxins. In some patients with severe AKI, initiation of renal replace- (Continued) ment therapy (RRT) may be necessary to manage urgent
gence of CKD, and patients who had preexisting CKD should ¢ Renal replacement therapy is used to manage the urgent be evaluated for worsening function. complications of severe acute kidney injury, including hyperkalemia, metabolic acidosis, volume overload refractory to diuretics, uremic manifestations, and dia- Renal Replacement Therapy lyzable toxins. In some patients with severe AKI, initiation of renal replace- (Continued) ment therapy (RRT) may be necessary to manage urgent 69
Kidney Stones HVC e There is no proven benefit to early administration of renal ¢ Noncontrast helical CT is the gold standard modality to replacement therapy versus timing based on usual clinical diagnose nephrolithiasis; kidney ultrasonography can criteria in critically ill patients or those with sepsis. be used in pregnant women or when CT is unavailable. Types of Kidney Stones Kidney Stones See Table 30 for details on kidney stones and Table 3 for images of crystals. Overview Approximately 7% to 11% of the U.S. population will develop nephrolithiasis, and 50% will have recurrent disease. Risk fac- TABLE 30. Kidney Stone Risk Factors and Therapy tors for developing kidney stones include male sex, older age, | Stone Type _ Risk Factors Therapy White race, obesity, diabetes mellitus, the metabolic syndrome, decreased fluid intake, chronic diarrheal states, and Roux-en- Calcium Clinical: hyperpara- _ Increase fluids | | oxalate thyroidism; fat Hass | Y gastric bypass. Previous antibiotic use is also associated with | faslausonvacn: Decrease sodium intake | an increased risk for stone formation. | excessive vitamin D Decrease animal or C intake protein intake
Types of Kidney Stones Kidney Stones See Table 30 for details on kidney stones and Table 3 for images of crystals. Overview Approximately 7% to 11% of the U.S. population will develop nephrolithiasis, and 50% will have recurrent disease. Risk fac- TABLE 30. Kidney Stone Risk Factors and Therapy tors for developing kidney stones include male sex, older age, | Stone Type _ Risk Factors Therapy White race, obesity, diabetes mellitus, the metabolic syndrome, decreased fluid intake, chronic diarrheal states, and Roux-en- Calcium Clinical: hyperpara- _ Increase fluids | | oxalate thyroidism; fat Hass | Y gastric bypass. Previous antibiotic use is also associated with | faslausonvacn: Decrease sodium intake | an increased risk for stone formation. | excessive vitamin D Decrease animal or C intake protein intake Biochemical: Maintain adequate Clinical Manifestations | hypercalciuria; dietary calcium | hyperoxaluria; ! Although kidney stones may be asymptomatic and diagnosed | hypocitraturia Low oxalate diet | as an incidental finding on imaging, the typical presentation is | Thiazide diuretics waxing and waning “colicky” flank pain that radiates to the |
Biochemical: Maintain adequate Clinical Manifestations | hypercalciuria; dietary calcium | hyperoxaluria; ! Although kidney stones may be asymptomatic and diagnosed | hypocitraturia Low oxalate diet | as an incidental finding on imaging, the typical presentation is | Thiazide diuretics waxing and waning “colicky” flank pain that radiates to the | | Potassium citrate or groin. Nausea, vomiting, and dysuria may also be present. bicarbonate Microscopic hematuria is usually noted, although its absence | Calcium Clinical: distal renal _ Increase fluids does not exclude a stone. | phosphate __ tubular acidosis; D dienes Weak hyporparatayraiclnn: ecrease sodium intake | Similar symptoms may be present in pyelonephritis and carbonic anhydrase — Decrease animal acute abdominal processes, which need to be considered. In | inhibitors protein intake addition, the ureteral passage of blood clots can cause renal colic pain. | Biochemical: Maintain adequate | elevated urine pH; dietary calcium hypercalciuria; - —_ hypocitraturia Thiazide diuretics e Kidney stones typically present with waxing and waning Treat “colicky” flank pain that radiates to the groin; nausea, hyperparathyroidism
| Potassium citrate or groin. Nausea, vomiting, and dysuria may also be present. bicarbonate Microscopic hematuria is usually noted, although its absence | Calcium Clinical: distal renal _ Increase fluids does not exclude a stone. | phosphate __ tubular acidosis; D dienes Weak hyporparatayraiclnn: ecrease sodium intake | Similar symptoms may be present in pyelonephritis and carbonic anhydrase — Decrease animal acute abdominal processes, which need to be considered. In | inhibitors protein intake addition, the ureteral passage of blood clots can cause renal colic pain. | Biochemical: Maintain adequate | elevated urine pH; dietary calcium hypercalciuria; - —_ hypocitraturia Thiazide diuretics e Kidney stones typically present with waxing and waning Treat “colicky” flank pain that radiates to the groin; nausea, hyperparathyroidism vomiting, and dysuria may also be present. Potassium citrate or bicarbonate
| Potassium citrate or groin. Nausea, vomiting, and dysuria may also be present. bicarbonate Microscopic hematuria is usually noted, although its absence | Calcium Clinical: distal renal _ Increase fluids does not exclude a stone. | phosphate __ tubular acidosis; D dienes Weak hyporparatayraiclnn: ecrease sodium intake | Similar symptoms may be present in pyelonephritis and carbonic anhydrase — Decrease animal acute abdominal processes, which need to be considered. In | inhibitors protein intake addition, the ureteral passage of blood clots can cause renal colic pain. | Biochemical: Maintain adequate | elevated urine pH; dietary calcium hypercalciuria; - —_ hypocitraturia Thiazide diuretics e Kidney stones typically present with waxing and waning Treat “colicky” flank pain that radiates to the groin; nausea, hyperparathyroidism vomiting, and dysuria may also be present. Potassium citrate or bicarbonate Uric acid Clinical: the Increase fluids Diagnosis | metabolic ayncirommeraalit ee BS cae rate or ee
Uric acid Clinical: the Increase fluids Diagnosis | metabolic ayncirommeraalit ee BS cae rate or ee Nephrolithiasis should be considered in all patients who present | diarrheal illnesses; icerponate with flank pain. Costovertebral angle tenderness may be present. | metabolic acidosis Acetazolamide Microscopic examination of the urine for hematuria, leukocytes Biochemical: low Allopurinol that may indicate infection, pH measurement, and crystals is urine pH; hyperuricosuria mandatory, but findings are nonspecific. The presence of crystals may help to identify the type of stone (see Table 3). A complete Struvite Clinical: chronic Treat infection urinary tract Ussianiaiat ti blood count and complete metabolic panel should be obtained infections with urea- LOIEPISINEINENUON to exclude infection and acute kidney injury, and to screen for splitting organisms common metabolic causes of stone disease. Biochemical: Definitive diagnosis is made with imaging. Noncontrast elevated urine pH |
Microscopic examination of the urine for hematuria, leukocytes Biochemical: low Allopurinol that may indicate infection, pH measurement, and crystals is urine pH; hyperuricosuria mandatory, but findings are nonspecific. The presence of crystals may help to identify the type of stone (see Table 3). A complete Struvite Clinical: chronic Treat infection urinary tract Ussianiaiat ti blood count and complete metabolic panel should be obtained infections with urea- LOIEPISINEINENUON to exclude infection and acute kidney injury, and to screen for splitting organisms common metabolic causes of stone disease. Biochemical: Definitive diagnosis is made with imaging. Noncontrast elevated urine pH | helical CT is the gold standard modality because of its high | Cystine Clinical: strong Increase fluids sensitivity and specificity. Although less sensitive than CT, family history; Potassium citrate or young age at onset kidney ultrasonography is less expensive, has no radiation bicarbonate exposure, and can be used in pregnant women or when CT is Biochemical: Acetazolamide elevated urine unavailable. Plain abdominal radiography has a low sensitivity cystine; low urine Penicillamine and should not be ordered except to follow the stone burden in pH Tiopronin | established disease.
helical CT is the gold standard modality because of its high | Cystine Clinical: strong Increase fluids sensitivity and specificity. Although less sensitive than CT, family history; Potassium citrate or young age at onset kidney ultrasonography is less expensive, has no radiation bicarbonate exposure, and can be used in pregnant women or when CT is Biochemical: Acetazolamide elevated urine unavailable. Plain abdominal radiography has a low sensitivity cystine; low urine Penicillamine and should not be ordered except to follow the stone burden in pH Tiopronin | established disease. 70
Kidney Stones Calcium Cystine Eighty percent of kidney stones contain calcium; most are Cystine stones (1%-2% of stones) result from cystinuria, an composed of calcium oxalate, and the remainder are com- autosomal recessive disease that presents at a young age. These posed of calcium phosphate or a combination of the two. stones are recognized by characteristic hexagonal crystals in Calcium oxalate stones are associated with hypercalciuria, the urine (see Table 3). They may also form staghorn calculi hyperoxaluria, and hypocitraturia. Up to 50% of patients with and are less radio-opaque than calcium-containing stones. recurrent stones have elevated 24-hour urine calcium levels. This may be secondary to elevated serum calcium as seen in e Eighty percent of kidney stones contain calcium; most hyperparathyroidism, sarcoidosis, or excessive vitamin D are composed of calcium oxalate, which is associated intake, but is more frequently idiopathic. Hyperoxaluria can be with hypercalciuria, hyperoxaluria, and hypocitraturia. primary or can occur secondary to increased dietary oxalate intake or absorption; decreased calcium in the gastrointestinal e Staghorn calculi are the result of infection by urea- tract (as occurs with a low-calcium diet); or binding of calcium splitting bacteria such as Proteus, Klebsiella, or, less to fatty acids (as occurs with malabsorption syndromes). It can frequently, Pseudomonas species and can lead to both
Calcium Cystine Eighty percent of kidney stones contain calcium; most are Cystine stones (1%-2% of stones) result from cystinuria, an composed of calcium oxalate, and the remainder are com- autosomal recessive disease that presents at a young age. These posed of calcium phosphate or a combination of the two. stones are recognized by characteristic hexagonal crystals in Calcium oxalate stones are associated with hypercalciuria, the urine (see Table 3). They may also form staghorn calculi hyperoxaluria, and hypocitraturia. Up to 50% of patients with and are less radio-opaque than calcium-containing stones. recurrent stones have elevated 24-hour urine calcium levels. This may be secondary to elevated serum calcium as seen in e Eighty percent of kidney stones contain calcium; most hyperparathyroidism, sarcoidosis, or excessive vitamin D are composed of calcium oxalate, which is associated intake, but is more frequently idiopathic. Hyperoxaluria can be with hypercalciuria, hyperoxaluria, and hypocitraturia. primary or can occur secondary to increased dietary oxalate intake or absorption; decreased calcium in the gastrointestinal e Staghorn calculi are the result of infection by urea- tract (as occurs with a low-calcium diet); or binding of calcium splitting bacteria such as Proteus, Klebsiella, or, less to fatty acids (as occurs with malabsorption syndromes). It can frequently, Pseudomonas species and can lead to both also occur after Roux-en-Y gastric bypass surgery or with use sepsis and end-stage kidney disease. of the weight loss drug orlistat, which allows increased absorp- e Uric acid stones are radiolucent and are associated with tion of oxalate. High intake of vitamin C, which is metabolized chronic diarrhea, the metabolic syndrome, and gout. to oxalate, can also cause hyperoxaluria. Because citrate pre- e Cystine stones result from cystinuria, an autosomal vents calcium crystal formation, low urine levels are associated recessive disease that presents at a young age. with increased stone formation. Urinary citrate is decreased in the presence of metabolic acidosis, as occurs with chronic diar- rhea and distal renal tubular acidosis. Management Calcium phosphate stones occur when there is persis- Acute management of symptomatic nephrolithiasis is aimed at tently elevated urine pH and are associated with distal renal pain management and facilitation of stone passage. Pain can tubular acidosis, hyperparathyroidism, and carbonic anhy- be relieved by NSAIDs and opioids as needed. Stone passage drase inhibitors that increase urine pH, such as acetazolamide decreases with increasing size. Only 50% of stones >6 mm will or topiramate. pass, generally within 2 weeks, and stones >10 mm are extremely unlikely to pass spontaneously. The data concerning Struvite the use of medications such as tamsulosin, nifedipine, silodo- Struvite stones occur in the presence of urea-splitting bacteria sin, and tadalafil to enhance stone expulsion are controversial. such as Proteus, Klebsiella, or, less frequently, Pseudomonas But because there are few adverse effects attributed to these species. These bacteria split urea into ammonium, which medications, many experts recommend their use. markedly increases urine pH and results in the precipitation of Urologic intervention is required in all patients with evi- magnesium ammonium phosphate (struvite). The pH of the dence of infection, acute kidney injury, intractable pain, and urine will be >7.5. Struvite stones commonly produce stag- stones that fail to pass. This may necessitate shock wave litho- horn calculi (stones that bridge two or more renal calyces) and tripsy, ureteroscopy with laser ablation, or percutaneous occur most frequently in older women with chronic urinary nephrolithotomy. tract infections. Because struvite stones are large and grow Patients should strain their urine to collect stone frag- rapidly, they do not pass into the ureter to cause pain typical of ments for chemical analysis if the type of stone is unknown. In smaller stones. Signs and symptoms typically are related to the addition to the initial evaluation previously described, a underlying infection. Struvite staghorn calculi should be 24-hour urine collection for measurement of volume, calcium, removed to avoid increased morbidity from sepsis and end- oxalate, citrate, uric acid, and sodium should be obtained from stage kidney disease. all patients with recurrent stones. Increased fluid intake is the most important intervention Uric Acid to prevent recurrent disease regardless of stone composition. Uric acid stones (<10% of stones) develop in the presence of a per- Urine output should be >2500 mL/d to decrease urine solute sistently acidic urine, which decreases the solubility of uric acid. concentration. In addition, some individuals overproduce urate, resulting in Other interventions should be based on findings in the increased urine uric acid; both gout and hyperuricemia are asso- metabolic evaluation and stone analysis (see Table 30). If ciated with uric acid stones but are not always present. Chronic hypercalciuria is present, calcium excretion can be diarrhea, resulting in metabolic acidosis and low urine volume, is decreased by the use of thiazide diuretics. Because calcium a common cause of uric acid stones. The metabolic syndrome is excretion parallels sodium excretion, limiting sodium intake also associated with uric acid stone formation. Uric acid stones are will also lower urine calcium. Limiting animal protein may radiolucent but are visualized on ultrasound and CT. also have a beneficial effect on lowering urine calcium.
also occur after Roux-en-Y gastric bypass surgery or with use sepsis and end-stage kidney disease. of the weight loss drug orlistat, which allows increased absorp- e Uric acid stones are radiolucent and are associated with tion of oxalate. High intake of vitamin C, which is metabolized chronic diarrhea, the metabolic syndrome, and gout. to oxalate, can also cause hyperoxaluria. Because citrate pre- e Cystine stones result from cystinuria, an autosomal vents calcium crystal formation, low urine levels are associated recessive disease that presents at a young age. with increased stone formation. Urinary citrate is decreased in the presence of metabolic acidosis, as occurs with chronic diar- rhea and distal renal tubular acidosis. Management Calcium phosphate stones occur when there is persis- Acute management of symptomatic nephrolithiasis is aimed at tently elevated urine pH and are associated with distal renal pain management and facilitation of stone passage. Pain can tubular acidosis, hyperparathyroidism, and carbonic anhy- be relieved by NSAIDs and opioids as needed. Stone passage drase inhibitors that increase urine pH, such as acetazolamide decreases with increasing size. Only 50% of stones >6 mm will or topiramate. pass, generally within 2 weeks, and stones >10 mm are extremely unlikely to pass spontaneously. The data concerning Struvite the use of medications such as tamsulosin, nifedipine, silodo- Struvite stones occur in the presence of urea-splitting bacteria sin, and tadalafil to enhance stone expulsion are controversial. such as Proteus, Klebsiella, or, less frequently, Pseudomonas But because there are few adverse effects attributed to these species. These bacteria split urea into ammonium, which medications, many experts recommend their use. markedly increases urine pH and results in the precipitation of Urologic intervention is required in all patients with evi- magnesium ammonium phosphate (struvite). The pH of the dence of infection, acute kidney injury, intractable pain, and urine will be >7.5. Struvite stones commonly produce stag- stones that fail to pass. This may necessitate shock wave litho- horn calculi (stones that bridge two or more renal calyces) and tripsy, ureteroscopy with laser ablation, or percutaneous occur most frequently in older women with chronic urinary nephrolithotomy. tract infections. Because struvite stones are large and grow Patients should strain their urine to collect stone frag- rapidly, they do not pass into the ureter to cause pain typical of ments for chemical analysis if the type of stone is unknown. In smaller stones. Signs and symptoms typically are related to the addition to the initial evaluation previously described, a underlying infection. Struvite staghorn calculi should be 24-hour urine collection for measurement of volume, calcium, removed to avoid increased morbidity from sepsis and end- oxalate, citrate, uric acid, and sodium should be obtained from stage kidney disease. all patients with recurrent stones. Increased fluid intake is the most important intervention Uric Acid to prevent recurrent disease regardless of stone composition. Uric acid stones (<10% of stones) develop in the presence of a per- Urine output should be >2500 mL/d to decrease urine solute sistently acidic urine, which decreases the solubility of uric acid. concentration. In addition, some individuals overproduce urate, resulting in Other interventions should be based on findings in the increased urine uric acid; both gout and hyperuricemia are asso- metabolic evaluation and stone analysis (see Table 30). If ciated with uric acid stones but are not always present. Chronic hypercalciuria is present, calcium excretion can be diarrhea, resulting in metabolic acidosis and low urine volume, is decreased by the use of thiazide diuretics. Because calcium a common cause of uric acid stones. The metabolic syndrome is excretion parallels sodium excretion, limiting sodium intake also associated with uric acid stone formation. Uric acid stones are will also lower urine calcium. Limiting animal protein may radiolucent but are visualized on ultrasound and CT. also have a beneficial effect on lowering urine calcium. 71