Free-radical-mediated postischemic reperfusion injury in the kidney.
Acute tubular necrosis is a frequent occurrence following hypovolemic shock and human renal transplantation. Although this postischemic injury was originally thought to result from ischemia alone, it has recently been recognized that significant tissue injury can occur during the period of reperfusion. The demonstration of the oxygen free-radical-mediated postischemic reperfusion injury by Granger, Rutili, and McCord in ischemic cat intestine suggested that this mechanism might also be operative following renal ischemia. In the kidney, postischemic injury results in necrosis of the proximal renal tubule and accumulation of erythrocytes in the outer renal medulla. It has been proposed that the primary event leading to these pathologic changes is a free-radical-mediated injury to the endothelial cells in the inner stripe of the outer medulla. Experimental evidence in animals subjected to warm and cold ischemia supports a free-radical-mediated mechanism. The clinical significance of these findings is demonstrated in preclinical animal studies of renal transplantation in which approximately two-thirds of the injury following cold ischemia could be ablated by superoxide dismutase administered just prior to reperfusion or by allopurinol when administered both at the time of preservation and reperfusion or at the time of preservation alone.
Ratych
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Bulkley
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GB
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D002415:Cats; D005609:Free Radicals; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D016030:Kidney Transplantation; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000503:physiopathology*; D010477:Perfusion; D011183:Postoperative Complications; D011817:Rabbits; D051381:Rats; D012769:Shock / Q000150:complications; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013696:Temperature; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D005609:Free Radicals; D000493:Allopurinol; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase