The pathophysiology behind acute renal failure (ARF) is complex and only partly understood. Many data come from animal models where acute tubular necrosis is induced by transiently clamping a renal artery. Real patients are more complex, where renal failure is often part of a developing multisystem illness. The outer medulla is relatively hypoxic and prone to injury. When there is an ischaemic or septic insult, inflammatory mediators damage the endothelium. It is not as simple as damaged tubular cells sloughing and blocking the collecting ducts; there is a complex response Involving programmed cell death (apoptosis) and damage to the actin cytoskeleton, which facilitates cell-to-cell adhesion and forms the barrier between blood and filtrate. Genetic factors also play a role. "Knockout" mice without the gene for a cell adhesion molecule ICAM-1 (which helps leukocytes bind to the endothelium) do not develop ARF after an ischaemic insult.
Ischaemic or nephrotoxic acute tubular necrosis (ATN) accounts for 80-90% perioperative renal failure. A prospective multicentre study in Madrid in 1998 showed that out of 253 cases of acute renal failure in ICU, 76% were due to ATN, 18% due to a prerenal cause, and only two cases due to obstruction. In the critically ill, glomerulonephritis as a cause of acute renal failure is uncommon.
In animal models, interruption of blood flow for less than 25 minutes results in oliguria but no anatomical changes and renal function returns to normal; 60-120 minutes of interrupted blood flow causes tubular cell damage. These are the metabolically active cells. Renal recovery can occur if further insults are avoided. Interruption of blood blow for over 120 minutes causes renal infarction and irreversible acute renal failure. High risk surgical procedures for the development of acute renal failure are cardiac surgery, vascular surgery, biliary and hepatic surgery (because bile salts bind endotoxins, which cause renal vasoconstriction, and this action ceases in cholestasis), urological surgery, and procedures associated with intra-abdominal hypertension.
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