Buy the Book PDA Download

Update Me E-mail alerts The Merck Manual Minute

Print This Topic Email This Topic

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.

Acute Tubular Necrosis

Causes of acute tubular necrosis (ATN) include the following:

• Hypotension (ischemic ATN, common)
• Nephrotoxins (common)
• Sepsis (common)
• Major surgery
• Third-degree burns covering > 15% of BSA
• The heme pigments myoglobin and hemoglobin (uncommon)
• Disorders resulting in other endogenous toxins, such as tumor lysis or multiple myeloma (uncommon)
• 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:

• Aminoglycoside antibiotics
• Amphotericin B Some Trade Names
  ABELCET
  AMBISOME
  AMPHOCIN
  AMPHOTEC
  Click for Drug Monograph
  
• Cisplatin Some Trade Names
  PLATINOL
  Click for Drug Monograph
  
• Radiocontrast (particularly agents with osmolality > 100 mL)
• NSAIDs

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 Some Trade Names
ABELCET
AMBISOME
AMPHOCIN
AMPHOTEC
Click for Drug Monograph
) 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:

• Baseline creatinine clearance < 47 mL/min
• Diabetes mellitus
• Preexisting hypovolemia or poor renal perfusion

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

• 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 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).

Table 1
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 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 the setting of chronic renal failure and recent diuretic use.

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

• Supportive care

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 Some Trade Names
OSMITROL
RESECTISOL
Click for Drug Monograph
or dopamine Some Trade Names
INTROPIN
Click for Drug Monograph
. General management of acute renal failure is discussed elsewhere in The Manual (see Renal Failure: Treatment).

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 Some Trade Names
OSMITROL
RESECTISOL
Click for Drug Monograph
, or dopamine Some Trade Names
INTROPIN
Click for Drug Monograph
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:

• Older age
• Preexisting renal insufficiency (eg, serum creatinine > 1.5 mg/dL)
• Diabetes mellitus
• Heart failure
• Multiple myeloma
• High doses (eg, > 100 mL) of a 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

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:

• Delay in onset of increased creatinine > 48 h after the procedure
• Presence of other atheroembolic findings (eg, in skin, toes)
• Persistently poor renal function
• Transient eosinophilia or eosinophiluria and low complement levels (measured if atheroemboli are seriously considered)

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 Some Trade Names
MUCOMYST
Click for Drug Monograph
is an antioxidant that may be helpful; protocols vary, but acetylcysteine Some Trade Names
MUCOMYST
Click for Drug Monograph
, 600 mg po bid the day before and the day of the procedure, may be given, combined with NaCl infusion. Acetylcysteine Some Trade Names
MUCOMYST
Click for Drug Monograph
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