Apoptotic mechanisms in acute renal failure

It has been generally accepted that a catastrophic breakdown of regulated c ellular homeostasis, known as necrosis, is the mode of cellular injury in v arious forms of acute renal failure. One of the major advances in our under standing of cell death has been the recognition that the pathways tradition ally associated with apoptosis as described in the landmark study by Kerr, Wyllie, and Currie in 1972 may be very critical in the form of cell injury associated with necrosis. The pathway that is followed by the cell varies w ith both nature and severity of insults and may evolve from an apoptotic to a necrotic form of cell death. It is also likely that there are some commo n pathways that are shared and regulated in the two modes of cell death. In this review, we first describe evidence for the role of apoptotic pathways in ischemic acute renal failure, and then consider the potential mechanism s that may participate in this model of acute renal tubular injury. We then summarize the current information of apoptotic pathways related to other c ommon causes of acute renal failure including endotoxin-induced, toxic acut e renal failure and transplant rejection. A better understanding of the mec hanisms of apoptosis could lead to safer and more specific therapeutic inte rventions for acute renal failure. Am J Med. 2000;108: 403-415. (C) 2000 by Excerpta Medica, Inc.