Impact of ischemia/reperfusion injury and early inflammatory responses in kidney transplantation

Ischemia/reperfusion injury (IRI) is an unavoidable consequence of organ transplantation that may occur during a number of stages in the transplantation procedure. Ischemia necessarily occurs after procurement of the organ and cold preservation but may be initiated in cadaver donors around the time of brain death as a result of cardiovascular instability. In this review, we examine the evidence suggesting that IRI in renal transplantation induces an acute inflammatory response involving the generation of reactive oxygen species, endothelial dysfunction, and induction of proinflammatory molecules. This process leads to the recruitment of platelets and neutrophils and the upregulation of molecules that ultimately increase the immunogenicity of a transplant. This nonspecific inflammatory response can prime the organ for alloimmune responses, thus contributing adversely to delayed graft function, allograft rejection, and long-term survival. A.variety of immunohistologic and molecular techniques have been developed that may be used to determine potential markers of IRI. Interventional therapies designed to inhibit the harmful effects of superoxide generation and leukocyte-endothelial interactions may limit this early damage and improve organ quality for transplantation. Copyright © 2000 by W.B. Saunders Company.