Author(s): Pratschke J, Tullius SG, Neuhaus P
Purpose of review: The donor-associated risk factor of brain death is closely associated with ischemia and reperfusion injury. This article outlines the interference between brain death–induced graft alterations and conditions after reperfusion injury during the pretransplantation and early posttransplantation periods.
Recent findings: Unrelated living donor kidney transplants have a better long-term outcome than cadaver donor grafts despite a poorer human lymphocyte antigen match. Prolonged cold ischemia in cadaver donors has been identified as one important risk factor influencing graft outcome. In addition to its nonspecific injury effects, it enhances graft immunogenicity and host alloresponsiveness. Occurring early in the transplant process, it initiates a cascade of molecular and cellular events, including the release of proinflammatory mediators and attraction of various cell types infiltrating the tissues. As a consequence, acute and chronic changes develop that influence the structure and function of the organ, which may contribute to reduced graft survival. Originally considered an event surrounding organ procurement, preservation, and revascularization, it has recently been associated with donor conditions such as brain death. Experimental data have shown that brain death is an independent risk factor that induces similar pathophysiologic features as ischemia and reperfusion. Indeed, brain death–induced proinflammatory changes in donor organs show a pattern comparable to that seen after prolonged cold organ ischemia. Thus, brain death and ischemia and reperfusion injury can no be longer categorized as nonimmune, antigen-independent events.
Summary: Brain death and ischemia and reperfusion have a synergistic negative impact on long-term allograft outcome by enhancing graft immunogenicity and host alloresponsiveness. In the authors’ opinion, graft-preserving strategies should start shortly after brain death diagnosis to improve organ quality before the transplant procedure.