Current concepts in clinical therapeutics: drug therapy in acute renal failure

The etiology and classification, pathophysiology, diagnosis, clinical course, and drug therapy of acute renal failure (ARF) are reviewed. ARF, a rapid reduction in kidney function that results in decreased glomerular filtration rate and tubular function, is caused by many different factors and can cause multiple organ dysfunction. The major causes of ARF are classically divided into three broad categories: (1) prerenal, or hypoperfusion states, (2) intrarenal, or intrinsic renal parenchymal disease, and (3) post-renal, or urinary obstructive disorders. The underlying pathogenic abnormality is renal tubular cell damage in patients with prerenal azotemia; vascular and glomerular damage is often secondary to immunologic mechanisms. Interstitial nephritis, often drug-induced, results from an immunologically mediated inflammatory renal response. Obstructive nephropathy results from partial or complete blockade of urine flow. Diagnosis relies heavily on patient history and physical examination; laboratory data, renal imaging, and sometimes renal biopsy results can yield important clues. The clinical course of ARF consists of four phases: insult and onset, maintenance, diuresis, and recovery. Morbidity and mortality are high. Drug therapy is directed at preventing or reversing the renal lesion before ARF becomes established and supporting the patient to allow the body to correct the lesion once it occurs. Prevention of prerenal azotemia and intrarenal disease is directed at identifying patients at risk, minimizing nephrotoxicity, and maintaining adequate urine output. In patients with established renal failure, an appropriate intravascular volume and pressure must be re-established and underlying problems must be corrected. Fluid, electrolyte, and acid-base balance are critical, and other serious effects on the gastrointestinal and neurologic systems must be addressed. Even though morbidity and mortality remain unacceptably high in patients with acute renal failure, promising progress has been made during the last 20-30 years.