гострий тубулярний некроз (ATN)

Common causes of acute tubular necrosis include the following:

• Renal hypoperfusion, most often caused by hypotension or sepsis (ischemic ATN; most common, especially in patients in an intensive care unit)

• Nephrotoxins

• Major surgery (often due to multiple factors)

Other causes of ATN include

• Third-degree burns covering > 15% of body surface area

• The heme pigments myoglobin and hemoglobin (caused by either rhabdomyolysis or massive hemolysis)

• Other endogenous toxins, resulting from disorders such as tumor lysis or multiple myeloma

• Poisons, such as ethylene glycol

• Herbal and folk remedies, such as ingestion of fish gallbladder in Southeast Asia

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 Contrast Nephropathy)

• Nonsteroidal anti-inflammatory drugs (NSAIDs; especially when concurrent with poor renal perfusion or other nephrotoxic agents)

• Colistimethate (colistin)

• Calcineurin inhibitors (eg, cyclosporine, tacrolimus, used systemically)

• Vancomycin (particularly with supratherapeutic dosing [1])

Massive volume loss, particularly in patients with septic or hemorrhagic shock, pancreatitis, or major surgery, increases the risk of ischemic ATN; patients with serious comorbidities are at highest risk.

Major surgery and advanced hepatobiliary disease (2) 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.

Acute tubular necrosis is more likely to develop in patients with the following:

• Preexisting chronic kidney disease

• Diabetes mellitus

• Preexisting hypovolemia or poor renal perfusion

• Older age

Acute tubular necrosis is usually asymptomatic but may cause symptoms or signs of acute kidney injury, typically oliguria initially, if ATN is severe. However, urine output may not be reduced if ATN is less severe (eg, typical in aminoglycoside-induced ATN).

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

Acute tubular necrosis is suspected when serum creatinine rises ≥ 0.3 mg/dL/day (26.5 micromol/liter [μmol/L]) above baseline or a 1.5- to 2.0-fold increase in serum creatinine from 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 blood urea nitrogen (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, gastrointestinal 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 acute tubular necrosis from prerenal azotemia (see table Laboratory Findings Distinguishing Acute Tubular Necrosis From Prerenal Azotemia).

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 weeks. In sick patients, even when acute kidney injury is mild, morbidity and mortality are increased. Prognosis is better in patients who do not require treatment in an intensive care unit (32% mortality) than in those who do (72% mortality). Predictors of mortality include mainly

• Decreased urine volume (eg, anuria, oliguria)

• Severity of the underlying disorder

• Severity of coexisting disorders

Patients who survive acute tubular necrosis have an increased risk of chronic kidney disease.

Cause of death is usually infection or the underlying disorder.

• 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 acute tubular necrosis 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 elsewhere.

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 glucose levels

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