Acute renal failure in man: pathogenesis in light of new morphological data.

The pathogenesis of acute renal failure (ARF) in such common conditions as acute tubular necrosis, acute interstitial nephritis, and primary graft anuria (ischemic transplant ARF) is poorly understood. Animal models may not exactly mimic the situation in man and thus human morphologic studies are of particular importance. Non-replacement of individual sloughed tubular cells and simplification of the brush border and basolateral infoldings of tubular cells are prominent morphologic changes which correlate with the presence of renal failure. It is possible that the initial injury inhibits cell membrane synthesis, thus interfering with proximal tubular sodium reabsorption with resulting activation of the renin angiotensin system and afferent arteriolar vasoconstriction. Tubular backleak, tubular obstruction by casts and debris, and decreased glomerular ultrafiltration coefficient may also play a role. Although poorly studied until now, the renal failure in primary graft anuria may have a completely different pathogenesis from that in acute tubular necrosis and acute interstitial nephritis. Cyclosporine nephrotoxicity is an important component of primary graft anuria, as seen in many transplant centers in the 1980's.