Role of leukocytes and leukocyte adhesion molecules in renal ischemic-reperfusion injury

Hamid Rabb, M.D.

Division of Nephrology and Hypertension, J. A. Haley VA Hospital & University of South Florida, Tampa, FL 33612

Received 12/07/95; Accepted 12/25/95; On-line 1/1/95

2. Introduction

Renal transplantation is the preferred treatment for end-stage renal disease. From the time of procurement of the kidney from the donor until the time that vascular anastomosis has been established in the recipient, the blood flow to the kidney is interrupted. The incidence of the postischemic allograft injury during the first post-operative week is about 30-40% (1). Such injury contributes to delayed graft dysfunction as well (1). Native kidneys also undergo ischemic acute renal failure which is associated with a mortality rate of upto 50% (2). Despite the development of dialysis this mortality rate has not improved in the last 30 years (2). This poor clinical outcome has given impetus to investigate mechanisms of post-ischemic renal failure and to develop novel strategies for its therapy.

Ischemia to the kidney triggers complex pathophysiologic responses so that restoration of normal renal blood flow soon after an ischemic insult may not prevent the development of processes that perpetuate tissue damage (3). Redistribution of renal blood flow, tubular lumen obstruction, tubular cell swelling, and most recently, apoptosis, are some of the processes thought to perpetuate the postischemic renal damage (2,3). The production of reactive oxygen species (ROS) has also been implicated in renal ischemic reperfusion injury (IRI), however the source of these ROS has not been defined thus far (4). Possible sources of ROS include infiltrating neutrophils, mitochondria and peroxisomes, while enzymes that generate ROS include xanthine oxidase and prostaglandin synthetase (4). In addition to the production of ROS, leukocytes can produce arachidonic acid metabolites, proteases, and other deleterious agents (5). In this manuscript the role of leukocytes and leukocyte-endothelial adhesion molecules in the pathogenesis of renal IRI is reviewed.