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Acute
tubular necrosis is kidney injury characterized by acute tubular
cell injury and dysfunction. 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, severe sepsis, or drug exposure
and is distinguished from prerenal azotemia by laboratory testing
and response to volume expansion. Treatment is supportive.
Causes of acute tubular necrosis (ATN) include the following:
Common nephrotoxins include the following:
Massive volume loss, particularly in patients with septic or hemorrhagic shock or pancreatitis or in patients who have had serious surgery, increases the risk of ischemic ATN; patients with serious comorbidities are at highest risk. Serious surgery and advanced hepatobiliary disease, poor perfusion states, and advanced age increase the risk of aminoglycoside toxicity. Certain drug combinations (eg, aminoglycosides with amphotericin B ) may be especially nephrotoxic. NSAIDs may cause several types of intrinsic kidney disease, including ATN. Toxic exposures cause patchy, segmental, tubular luminal occlusion with casts and cellular debris or segmental tubular necrosis.
ATN is more likely to develop in patients with the following:
Symptoms and Signs
ATN is usually asymptomatic but may cause symptoms or signs of acute renal failure, typically oliguria (see Approach to the Critically Ill Patient: Oliguria) initially.
Diagnosis
ATN is suspected when serum creatinine rises ≥ 0.5 mg/dL/day above baseline after an apparent trigger (eg, hypotensive event, exposure to a nephrotoxin); the rise in creatinine may occur days after exposure to some nephrotoxins. ATN must be differentiated from prerenal azotemia because treatment differs. In prerenal azotemia, renal perfusion is decreased enough to elevate serum BUN out of proportion to creatinine, but not enough to cause ischemic damage to tubular cells. Prerenal azotemia can be caused by direct intravascular fluid loss (eg, from hemorrhage, GI tract or urinary losses) or by a relative decrease in effective circulating volume without loss of total body fluid (eg, in heart failure, portal hypertension with ascites). If fluid loss is the cause, volume expansion using IV normal saline solution normalizes serum creatinine level. If ATN is the cause, IV saline typically causes no rapid change in serum creatinine.
Laboratory findings also help distinguish ATN from prerenal azotemia (see Table 1: Tubulointerstitial Diseases: Laboratory Findings Distinguishing Acute Tubular Necrosis From Prerenal Azotemia ).
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Table 1
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Laboratory Findings 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 (usually < 350)
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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, or a combination
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Normal or with hyaline casts
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*Criteria may not apply in the setting of chronic renal failure and recent diuretic use.
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Prognosis
In otherwise healthy patients, prognosis is good when the underlying insult is corrected; serum creatinine typically returns to normal or near-normal within 1 to 3 wk. In sick patients, even when acute renal failure is mild, morbidity and mortality are increased; prognosis is better in patients who do not require ICU care (32% mortality) than in those who do (72% mortality). Predictors of mortality include mainly decreased urine volume (eg, anuria, oliguria) and severity of the underlying illness and comorbid disorders.
Cause of death is usually infection or the underlying disorder.
Treatment
Treatment is supportive and includes stopping of nephrotoxins whenever possible, maintenance of euvolemia, nutritional support, and treatment of infections (preferably with drugs that are not nephrotoxic). Diuretics are commonly used to maintain urine output in oliguric ATN but are of unproven benefit; there is no evidence to support use of mannitol or dopamine . General management of acute renal failure is discussed elsewhere in The Manual (see Renal Failure: Treatment).
Prevention
Prevention includes the following:
There is no evidence that loop diuretics, mannitol , or dopamine helps prevent ATN.
Contrast
Nephropathy
Contrast
nephropathy is worsening of renal function after IV administration
of radiocontrast and is usually temporary. Diagnosis is based on a
progressive rise in serum creatinine 24 to 48 h after contrast is
given. Treatment is supportive. Volume loading with isotonic saline
before and after contrast administration may help in prevention.
All iodinated radiocontrast agents are nephrotoxic. However, risk is lower with newer contrast agents, which have a lower osmolality than older agents, whose osmolality is about 1400 to 1800 mOsm/kg. For example, 2nd-generation, low-osmolal agents (eg, iohexol, iopamidol, ioxaglate) have an osmolality of about 500 to 850 mOsm/kg, which is still higher than blood osmolality. Iodixanol, the first of the even newer iso-osmolal agents, has an osmolality of 290 mOsm/kg, about equal to that of blood.
The precise mechanism of radiocontrast toxicity is unknown but is suspected to be some combination of renal vasoconstriction and direct cytotoxic effects, perhaps through formation of reactive O2 species, causing ATN.
Risk factors:
Risk factors for nephrotoxicity are the following:
Diagnosis
Diagnosis is based on a progressive rise in serum creatinine 24 to 48 h after a contrast study. Most patients have no symptoms. Renal function typically later returns to normal.
After femoral artery catheterization, contrast nephropathy may be difficult to distinguish from renal atheroembolism. Factors that can suggest renal atheroemboli include the following:
Treatment
Treatment is supportive.
Prevention
Prevention involves avoiding contrast when possible (eg, not using CT to diagnose appendicitis) and, when contrast is necessary, using the agent with the lowest osmolality for patients with risk factors. When contrast is given, mild volume expansion with isotonic NaCl (ie, 154 mEq/L) is recommended; 1 mL/kg/h is given beginning 6 to 12 h before contrast is given and continued for 6 to 12 h after the procedure. Infusion of NaHCO3 has no proven advantage over normal saline and may even be harmful. Nephrotoxic drugs are avoided before and after the procedure. Acetylcysteine is an antioxidant that may be helpful; protocols vary, but acetylcysteine , 600 mg po bid the day before and the day of the procedure, may be given, combined with NaCl 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 has no proven benefit compared with other less invasive strategies in preventing acute kidney injury in patients who have chronic kidney disease and who require high doses of contrast and also is not practical. Therefore, this procedure is not recommended. Patients undergoing regular hemodialysis for end-stage renal disease who require contrast do not need supplementary, prophylactic hemodialysis after the procedure.
Last full review/revision August 2009 by Navin Jaipaul, MD, MHS
Content last modified August 2009
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