Relationships between oxidant and non-oxidant mechanisms in the pathogenesis of acute renal failure.

During the past several years studies using freshly isolated proximal tubules in suspension have contributed to understanding several of the major cellular processes underlying ischemic and related forms of acute renal failure. Tubules have a large capacity to augment their intracellular ATP content when supplemented with exogenous purines. This process has been shown to be mostly explained by adenosine uptake. Reductions of cell pH such as occur prominently during ischemia strongly protect tubules against a variety of insults. Increases of cytosolic free calcium to micromolar levels are highly damaging to tubules and do occur prior to lethal cell injury induced by ATP-depleting metabolic inhibitors, but do not critically determine the outcome in the latter setting. Given their ubiquitous occurrence and well-documented importance in a variety of systems, reactive oxygen metabolites play a surprisingly small role in oxygen deprivation-induced injury to isolated tubules. Several small neutral amino acids, glycine being the prototype and most potent, have a critical, constitutive effect to maintain tubule cell structural integrity during a variety of acute insults.