(See also Overview of Tubulointerstitial Diseases Overview of Tubulointerstitial Diseases Tubulointerstitial diseases are clinically heterogeneous disorders that share similar features of tubular and interstitial injury. In severe and prolonged cases, the entire kidney may become... read more .)
Etiology of Acute Tubular Necrosis
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)
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 Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more or massive hemolysis Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span ( read more )
Other endogenous toxins, resulting from disorders such as tumor lysis Tumor Lysis and Cytokine Release Syndromes Adverse effects are common in patients receiving any cancer therapy. Patients may also have adverse effects resulting from their cancer. Successfully managing these adverse effects is important... read more or multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more
Poisons, such as ethylene glycol
Herbal and folk remedies, such as ingestion of fish gallbladder in Southeast Asia
Common nephrotoxins include the following:
Cisplatin and other chemotherapy drugs
Radiocontrast (particularly ionic high osmolar agents given IV in volumes > 100 mL—see Contrast Nephropathy 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 hours... read more )
Nonsteroidal anti-inflammatory drugs (NSAIDs; especially when concurrent with poor renal perfusion or other nephrotoxic agents)
Calcineurin inhibitors (eg, cyclosporine, tacrolimus, used systemically)
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) Etiology references 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... read more 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 hypovolemia or poor renal perfusion
Symptoms and Signs of Acute Tubular Necrosis
Acute tubular necrosis is usually asymptomatic but may cause symptoms or signs of acute kidney injury, typically oliguria Oliguria Oliguria is urine output read more initially, if ATN is severe. However, urine output may not be reduced if ATN is less severe (eg, typical in aminoglycoside-induced ATN).
Diagnosis of Acute Tubular Necrosis
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 Laboratory Findings Distinguishing Acute Tubular Necrosis From Prerenal Azotemia 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... read more ).
Prognosis for Acute Tubular Necrosis
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 Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more 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 Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more .
Cause of death is usually infection or the underlying disorder.
Treatment of Acute Tubular Necrosis
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 Treatment Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more is discussed elsewhere.
Pearls & Pitfalls
Prevention of Acute Tubular Necrosis
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
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.
Acute tubular necrosis (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.