Role of apoptosis in the pathogenesis of acute renal failure.
Renal tubular cells die by apoptosis as well as necrosis in experimental models of ischemic and toxic acute renal failure as well as in humans with acute tubular necrosis. It is not yet possible, however, to determine the relative contribution of these two forms of cell death to loss of renal tubular cells in acute tubular necrosis. The beneficial effect of administering growth factors to animals with acute tubular necrosis is probably related to the potent antiapoptotic (survival) effects of growth factors as well as to their proliferative effects. Rapamycin inhibits both of these effects of growth factors and delays the recovery of renal function after acute tubular necrosis by inhibiting renal tubular cell regeneration and by increasing renal tubular cell loss by apoptosis. The administration of caspase inhibitors ameliorates ischemia-reperfusion injury in multiple organs including the kidney. However, the extent to which this protective effect of caspase inhibition is caused by reduced intrarenal inflammation, or by amelioration of renal tubular cell loss due to apoptosis, remains uncertain. In addition to caspase inhibition, the apoptotic pathway offers many potential targets for therapeutic interventions to prevent renal tubular cell apoptosis.
Bonegio
Ramon
R
Renal Section, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Lieberthal
Wilfred
W
D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D002448:Cell Adhesion; D002945:Cisplatin / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000209:etiology; D007684:Kidney Tubules / Q000098:blood supply / Q000473:pathology; D009336:Necrosis; D020123:Sirolimus / Q000494:pharmacology
D061945:Caspase Inhibitors; D006133:Growth Substances; D006160:Guanosine Triphosphate; D002945:Cisplatin; D020123:Sirolimus