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Primer: Acute renal failure

From the March ACP Hospitalist, copyright © 2007 by the American College of Physicians.

Acute renal failure (ARF) may develop in response to decreased renal perfusion (prerenal ARF), obstruction (postrenal ARF) or intrinsic renal parenchymal injury (intrarenal ARF). Diagnosis of this condition first involves a clinical assessment, beginning with a thorough review of the history and medical record with a particular focus on nephrotoxic and hemodynamic insults (see Figure).

The clinical setting often suggests the cause of ARF. Recent exposure to a new medication or associated extrarenal manifestations may suggest the diagnosis. The history, physical examination and other laboratory and hemodynamic parameters are then used to accurately define the status of the extracellular fluid volume. Analysis of the fractional excretion of sodium (FE_Na), defined as the percent of the filtered load of sodium excreted in the urine, is the most commonly used parameter in assessing oliguric renal failure.

A FE_Na less than 1% suggests a prerenal cause of ARF, whereas a value more than 2% is consistent with epithelial tubular injury. The FE_Na must be interpreted carefully in the context of the history; physical examination; and other laboratory findings, such as analysis of the urine sediment, because more than one process commonly occurs simultaneously. The FE_Na, for example, may be low early in the course of ischemic tubular injury and urinary tract obstruction, as well as in radiocontrast-induced tubular injury. Conversely, diuretics can increase the FE_Na in patients with prerenal azotemia. The FE_Na usually is low in patients presenting with the nephrotic syndrome or glomerulonephritis.

Because obstruction is a reversible cause of renal failure, ultrasonography is indicated early in the evaluation. Microscopic analysis of the urine sediment is essential in ARF, particularly if pre- and postrenal causes have been excluded. If the diagnosis of intrarenal ARF remains unclear after reviewing the aforementioned data, renal biopsy should be considered. Vascular insults such as renal artery thrombosis of a solitary kidney or renal vein thrombosis also should be considered because timely intervention is critical to preserve renal function.

Key points

Acute prerenal failure

• Numerous medications, iodinated contrast agents, and hypercalcemia may reduce glomerular capillary pressure through afferent arteriolar vasoconstriction.
• Abdominal compartment syndrome is a form of prerenal ARF that develops in patients with an expanded extracellular fluid volume after massive fluid resuscitation.
• Surgical or percutaneous decompression of the abdomen usually causes a prompt return of renal function in patients with abdominal compartment syndrome.
• Treatment of prerenal azotemia in patients with true volume depletion consists of restoring the extracellular fluid volume to normal with isotonic saline.
• Management of patients with functional prerenal failure should focus on reversing the underlying cause.
• Medications suspected of decreasing the glomerular capillary pressure should be discontinued in functional prerenal ARF.

Acute postrenal failure

• The presence of hydronephrosis is 90% sensitive and specific for obstruction but may not be evident in patients with concurrent volume depletion or retroperitoneal fibrosis.
• Urinary tract obstruction is most common in men with prostatic hypertrophy or cancer and in patients with intra-abdominal and pelvic malignancies.
• The clinical presentation of urinary tract obstruction may vary from anuria to polyuria alternating with oliguria.
• Methotrexate, intravenous acyclovir, sulfadiazine and indinavir may cause obstruction of the renal tubule.
• Allopurinol prophylaxis has significantly decreased the incidence of urate nephropathy after induction of cancer chemotherapy.
• Early intervention with hemodialysis is indicated for ARF associated with tumor lysis syndrome.
• Urinary alkalinization has been advocated for the treatment of urate nephropathy but may worsen tubular obstruction by promoting formation of calcium phosphate crystals within the renal tubules.
• Rasburicase can be used to treat hyperuricemia associated with acute urate nephropathy.
• Rasburicase may be indicated as a prophylactic measure in patients with malignancies with a high proliferation rate.

Acute intrarenal failure

• Therapeutic agents are a common cause of ARF, and account for up to 30% of cases of intrarenal ARF in hospitalized patients.
• Ischemic tubular injury is the most common form of intrinsic renal injury in critically ill patients.
• Initial treatment of established ischemic tubular injury includes prevention of further renal parenchymal injury; correction of the inciting event, when possible; maintenance of fluid and electrolyte balance; and tight glycemic control.
• Aminoglycoside antibiotics are the most common cause of medication-induced renal failure.
• In aminoglycoside-induced acute tubular injury, cumulative uptake of the causative agent by the proximal tubular cells appears to be more important than trough levels in the development of nephrotoxicity.
• Aminoglycosides have been shown to exhibit less nephrotoxicity and equivalent efficacy when administered in higher doses on a once-daily basis.
• To prevent radiocontrast nephropathy, routine simultaneous renal arteriography in patients undergoing cardiac catheterization is discouraged.
• Volume expansion with isotonic saline or sodium bicarbonate is the most effective means of preventing radiocontrast nephropathy.
• An elevated serum creatine kinase level and heme positivity on urine dipstick in the absence of erythrocytes on microscopic analysis of the urine suggest rhabdomyolysis.
• The risk for renal failure increases when the serum creatine kinase level exceeds 5000 U/L.
• Expansion of the extracellular fluid volume with isotonic saline is the most effective measure to limit nephrotoxicity in rhabdomyolysis.
• Interstitial nephritis associated with NSAIDs and cyclooxygenase-2 inhibitors responds only minimally to corticosteroids.

Established acute renal failure

• Judicious fluid resuscitation and avoidance of further ischemic or nephrotoxic insults remain the mainstay of ARF therapy.
• Modifying drug dosing according to the degree of renal impairment and frequent monitoring of drug levels are indicated for patients with ARF.
• Indications for dialysis in patients with ARF include diuretic-resistant fluid overload, hyperkalemia, acidosis and uremic complications.
• Dialysis for ARF increasingly is initiated earlier, particularly in oliguric, critically ill patients.
• Stable patients with ARF expected to recover renal function within several days may benefit from restriction of fluids, sodium, potassium, phosphorus and protein to avoid the need for dialysis.

Adapted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 14).

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ACP Hospitalist provides news and information for internists about the practice of medicine and reports on the policies, products and activities of ACP. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated