Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes 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.

Acute Tubular Necrosis

Causes of ATN include the following:

• Renal hypoperfusion, most often caused by hypotension or sepsis (ischemic ATN; most common, especially in patients in an ICU)
• Nephrotoxins (common)
• Major surgery (common, often due to multiple factors)
• Third-degree burns covering > 15% of BSA (less common)
• The heme pigments myoglobin and hemoglobin (causing rhabdomyolysis, less common)
• Disorders resulting in other endogenous toxins, such as tumor lysis or multiple myeloma (less common)
• Poisons, such as ethylene glycol (uncommon)
• Herbal and folk remedies, such as ingestion of fish gallbladder in Southeast Asia (uncommon)

Common nephrotoxins include the following:

• Aminoglycosides
• Amphotericin B
• Cisplatin and other chemotherapy drugs
• Radiocontrast (particularly ionic high osmolar agents given IV in volumes > 100 mL—see Tubulointerstitial Diseases: Contrast Nephropathy)
• NSAIDs
• Colistimethate
• Calcineurin inhibitors (eg, cyclosporine, tacrolimus, used systemically)

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 older 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:

• Preexisting chronic kidney disease
• Diabetes mellitus
• Preexisting hypovolemia or poor renal perfusion
• Older age

Symptoms and Signs

ATN is usually asymptomatic but may cause symptoms or signs of acute kidney injury, typically oliguria (see Approach to the Critically Ill Patient: Oliguria) initially if ATN is severe. However, urine output may not be reduced if ATN is less severe (eg, typical in aminoglycoside-induced ATN).

Diagnosis

• Differentiation from prerenal azotemia, based mainly on laboratory findings and, in the case of blood or fluid loss, response to volume expansion

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 1 to 2 days after certain exposures (eg, IV radiocontrast) but be more delayed after exposure to other nephrotoxins (eg, aminoglycosides). 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, due to hemorrhage, GI tract losses, 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 increases urine output and normalizes serum creatinine level. If ATN is the cause, IV saline typically causes no increase in urine output and no rapid change in serum creatinine. Untreated prerenal azotemia may progress to ischemic ATN.

Laboratory findings also help distinguish ATN from prerenal azotemia (see Table 1: Tubulointerstitial Diseases: Laboratory Findings Distinguishing Acute Tubular Necrosis From Prerenal Azotemia).

Table 1
PrintOpen table in new window
Laboratory Findings Distinguishing Acute Tubular Necrosis From Prerenal Azotemia Test* Acute Tubular Necrosis Prerenal Azotemia Rate of creatinine rise 0.3–0.5 mg/dL/day Variable and fluctuates BUN/creatinine ratio 10–15:1 > 20:1 Urine osmolality (mOsm/kg) < 450 (usually < 350) > 500 Urine specific gravity ≤ 1.010 > 1.020 Urine Na (mEq/L) > 40 < 20 Urine/plasma creatinine ratio < 20 > 40 Fractional excretion of Na (%) > 2 < 1 Urinary sediment Muddy brown granular casts, epithelial cell casts, free epithelial cells, or a combination Normal or with hyaline casts *Criteria may not apply in patients with chronic kidney disease or recent diuretic use.

Prognosis

In otherwise healthy patients, short-term 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 disorder and comorbid disorders. Patients who survive ATN have an increased risk of chronic kidney disease.

Cause of death is usually infection or the underlying disorder.

Treatment

• Supportive care

Treatment is supportive and includes stopping nephrotoxins whenever possible, maintaining euvolemia, providing nutritional support, and treating infections (preferably with drugs that are not nephrotoxic). Diuretics may be used to maintain urine output in oliguric ATN but are of unproven benefit and do not alter the course of kidney injury; there is no evidence to support use of mannitol or dopamine. General management of acute kidney injury is discussed in Acute Kidney Injury: Treatment.

Pearls & Pitfalls Diuretics may improve urinary output in patients with ATN but do not alter the course of kidney injury.

Prevention

Prevention includes the following:

• Maintaining euvolemia and renal perfusion in critically ill patients
• Avoiding nephrotoxic drugs when possible
• Closely monitoring renal function when nephrotoxic drugs must be used
• Taking measures to prevent contrast nephropathy
• Among patients with diabetes, controlling blood sugar levels

There is no evidence that loop diuretics, mannitol, or dopamine helps prevent or alter the course of established ATN.

Key Points

• ATN can develop after various disorders or triggers decrease renal perfusion or expose the kidneys to toxins.
• Other than oliguria in severe cases, symptoms do not develop unless and until renal failure develops.
• Differentiate ATN from prerenal azotemia by the response to volume expansion and by urine and blood chemistry tests and calculations derived from them.
• Correct the cause of ATN as soon as possible to achieve a good short-term prognosis.
• Stop nephrotoxins, maintain euvolemia, and treat infection and undernutrition.

Last full review/revision March 2013 by Navin Jaipaul, MD, MHS