Mechanisms of acute renal failure

Abstract

Acute renal failure can be defined as an abrupt decline in renal function with a decrease in glomerular filtration rate (GFR) resulting in the retention of nitrogenous waste products. Acute renal failure has conventionally been classified as (a) prerenal failure, denoting a disorder in the systemic circulation that causes renal hypoperfusion. Implicit in the prerenal classification is that the correction of the underlying circulatory disturbance (e.g. by improvement in cardiac function or repletion of volume) restores the GFR. However, prerenal failure is often followed by transition to (b) intrinsic renal failure, where correction of the circulatory impairment does not restore the normal GFR. Intrinsic renal failure generally includes tubular necrosis. (c) Postrenal failure (obstructive) is a third possibility. Some patients with acute renal failure have oliguria (conventionally defined as a urine output of less than 400 ml day ), but others do not. In fact, patients with acute renal failure can be divided approximately equally into oliguric and non-oliguric. The pathogenetic factors appear to be identical in both types but in general are less severe in nonoliguric acute renal failure. Three abnormalities of renal function are present in intrinsic acute renal failure. These are (1) intratubular obstruction, (2) backleak of glomerular filtrate through damaged tubular epithelium, and (3) a primary reduction of GFR as a consequence of the release of vasoactive substances, which alter pressure, flow and filtration coefficient (kf) in the glomerular capillaries. The kidneys have an enormous blood supply. They receive 20–25 % of the cardiac output, but account for only 0.5 % of the body weight. The renal blood supply is typically around 400 ml 100 g 1 min 1 compared with about 70 ml 100 g 1 min 1 for heart and liver. The kidneys also have a very high oxygen consumption, but because of the high blood flow, the arteriovenous oxygen difference across the kidney is small. PO2 decreases from 95 mm Hg in the renal artery, to a value of about 70 mm Hg in the renal venous blood. In view of this it may seem surprising that renal ischaemia and acute renal failure are such major problems. In this article we examine those features of the renal physiology which contribute to the (intrinsic)