Acute renal failure: definition and pathogenesis.

Acute renal failure (ARF) in the critical care setting is defined as the abrupt decline in glomerular filtration rate (GFR) resulting from ischemic or toxic injury to the kidney. ARF is often only one of several organ-system failures that are present in this patient population. Recent evidence suggests that there are four major factors that are the most important in the initiation and maintenance of ARF. These include a decrease of glomerular capillary permeability, back-leak of glomerular filtrate, tubular obstruction, and intrarenal vasoconstriction. Both sub-lethal and lethal cell injury have been found in ARF, with the latter related either to necrosis or apoptosis. Intrarenal vasoconstriction, related to a shift in the balance between endothelin and endothelium-derived nitric oxide, is receiving considerable attention as a major contributor to the pathogenesis of ARF, with therapeutic maneuvers targeted at restoring the usual balance, and relieving intrarenal vasoconstriction. If such approaches prove to be of value, the outcome of patients with this serious condition might be substantially improved.