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Acute
tubular necrosis is characterized by acute tubular cell injury and
dysfunction causing renal insufficiency or failure. Common causes
are hypotension causing renal hypoperfusion and nephrotoxic drugs.
The condition is asymptomatic unless it causes renal failure. The
diagnosis is suspected when azotemia develops after a hypotensive
event or drug exposure and is distinguished from prerenal azotemia
by urine and blood chemistries. Treatment is supportive.
The most common causes of acute tubular necrosis (ATN) are hypotension and nephrotoxins. Common agents include aminoglycoside antibiotics, amphotericin, cisplatin , and radiocontrast (particularly > 100 mL). Major surgery and advanced hepatobiliary disease, poor perfusion states, and advanced age increase the risk of aminoglycoside toxicity. Less common causes include heme pigments (myoglobin and hemoglobin), poisons (ethylene glycol), and herbal and folk remedies (eg, ingestion of fish gallbladder in Southeast Asia). Certain drug combinations (eg, aminoglycosides with amphotericin B ) may be especially nephrotoxic. Toxic exposures cause patchy, segmental, tubular luminal occlusion with casts and cellular debris or segmental tubular necrosis. ATN is more likely to develop in those with a baseline creatinine clearance < 47 mL/min, diabetes mellitus, and preexisting hypovolemia or poor renal perfusion.
Symptoms,
Signs, and Diagnosis
ATN is usually asymptomatic but may cause symptoms or signs of acute renal failure (see Renal Failure: Acute Renal Failure (ARF)), at which time oliguria is common. The condition is suspected when serum creatinine rises ≥ 0.5 mg/dL/day above baseline after a hypotensive event or after exposure to a nephrotoxin; the rise in creatinine may occur days after exposure to some nephrotoxins. Criteria for distinguishing ATN from prerenal azotemia, important to determining treatment, are listed in
Table 1: Tubulointerstitial Diseases: Distinguishing Acute Tubular Necrosis From Prerenal Azotemia .
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Table 1
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Distinguishing Acute Tubular
Necrosis
From Prerenal Azotemia
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Test*
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Acute Tubular Necrosis
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Prerenal Azotemia
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Rate of creatinine rise
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0.3–0.5 mg/dL/day
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Variable and fluctuates
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BUN/creatinine ratio
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10–15:1
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> 20:1
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Urine osmolality (mOsm/kg)
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< 450
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> 500
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Urine Na (mEq/L)
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> 40
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< 20
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Urine/plasma creatinine ratio
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< 20
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> 40
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Fractional excretion of Na (%)
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> 2
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< 1
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Urinary sediment
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Muddy brown granular casts, epithelial cell casts, free epithelial cells
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Normal or with hyaline casts
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Response to saline expansion
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Variable, typically no immediate reduction in serum creatinine
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Serum creatinine normalizes in volume-depleted states
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*Criteria may not apply in the setting of chronic renal failure and recent diuretic use.
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Prognosis,
Treatment, and Prevention
Prognosis is good in otherwise healthy patients when the underlying insult is corrected; serum creatinine typically returns to normal or near-normal within 1 to 3 wk. In sick patients, even with mild acute renal failure, morbidity and mortality are increased; prognosis is better in a non-ICU (32% mortality) compared with an ICU (72% mortality) setting. Predictors of mortality include oliguria; high severity of illness; acute MI, stroke, or seizure; chronic immunosuppression; and the need for mechanical ventilation. Causes of death are usually infection or the underlying disease.
Treatment is supportive and includes discontinuation of nephrotoxins whenever possible, maintenance of euvolemia, and nutritional support. Diuretics are commonly used to maintain urine output in oliguric ATN but are of unproven benefit. Treatment of acute renal failure is discussed in Renal Failure: Treatment.
Prevention includes maintaining euvolemia and renal perfusion in critically ill patients, avoiding nephrotoxic drugs when possible and closely monitoring renal function when use is necessary, and taking various measures to avert contrast nephropathy (see below). Ineffective and possibly harmful agents include loop diuretics, dopamine , natriuretic peptides, and Ca channel blockers.
Contrast
Nephropathy
All iodinated radiocontrast agents are nephrotoxic. The precise mechanism of toxicity is unknown but is suspected to be some combination of renal vasoconstriction and ATN, perhaps through formation of reactive oxygen species. Risk factors for nephrotoxicity are older age, preexisting renal insufficiency (serum creatinine > 2 mg/dL), diabetes mellitus, heart failure, multiple myeloma, and high doses of hyperosmolar contrast agent (eg, during percutaneous coronary interventions). Factors that reduce renal perfusion, such as volume depletion or the concurrent use of NSAIDs or ACE inhibitors, also increase risk.
Diagnosis is based on a progressive rise in serum creatinine 24 to 48 h after a contrast study. Contrast nephropathy should be distinguished from renal atheroembolism, especially after femoral artery catheterization.
Treatment is supportive. Prevention involves mild volume expansion with NaHCO3, which is preferred over isotonic NaCl. The infusion is as 3 mL/kg/h of NaHCO3 at 154 mEq/L, beginning 1 h before contrast is given, followed by 1 mL/Kg/h for 6 h after the procedure. Nephrotoxic drugs are avoided before and after the procedure. Nonionic iso-osmolal contrast (eg, iodixanol) or nonionic low-osmolal contrast (eg, iohexol, iopamidol)—which has lower osmolality than ionic contrast but is still hyperosmolal relative to blood—is used. Acetylcysteine is an antioxidant that may be helpful; protocols vary, but it may be given 600 mg po bid the day before and the day of the procedure, combined with NaHCO3 infusion. Acetylcysteine and volume expansion may be most helpful in patients with mild preexisting renal disease and exposure to a low dose of contrast. Periprocedural continuous venovenous hemofiltration may be more effective at preventing acute renal failure in patients with chronic renal insufficiency who require high doses of contrast.
Last full review/revision November 2005
Content last modified May 2007
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