To what extent can limiting cold ischaemia/reperfusion injury prevent delayed graft function?

Renal injury may be caused by numerous factors, including ischaemia, toxins and autoimmune diseases. In recent years, chronic allograft nephropathy has become one of the main causes of late organ loss following transplantation. Several clinical and experimental studies have suggested that, in addition to alloantigen-dependent factors, several alloantigenindependent factors may be also involved in this process w1x. The most commonly accepted alloantigenindependent risk factors for chronic allograft nephropathy are cytomegalovirus infection, drug cytotoxicity, patient noncompliance, donor age, hyperlipidaemia and hypertension. These non-immunological factors certainly play an important part in the onset of chronic allograft nephropathy by directly damaging the transplanted kidney and also through their interaction with a variety of immune factors such as histo-incompatibility and acute rejection episodes. Non-immune renal injury of the kidney to be transplanted may also begin before the brain death of the donor and continue after transplantation w2x. Until recently, the impact of ischaemiaureperfusion injury (IRI), an antigen-independent event in the process of organ transplantation, on delayed graft function (DGF) and late allograft deterioration tended to be underestimated w3x. IRI is a complex sequence of events that involves depletion of cellular ATP, entry of calcium, sodium and water into cells, activation of endothelial cells and infiltration of neutrophils into ischaemic tissues w4x. The onset of non-specific inflammatory processes has been shown to initiate and modulate antigen-specific immunity w5x. The response to IRI closely resembles an immune response, and includes the upregulation of major histocompatibility complex (MHC) antigens w6x and adhesion molecules, and the production of cytokines and chemokines, leading to inflammatory infiltrates w7,8x. The exact role of IRI as an additional risk factor for DGF and kidney graft survival remains a matter of debate. Since the pig kidney seems to be the most attractive organ for xenotransplantation, we have developed an autotransplanted large pig kidney model to Correspondence and offprint requests to: A. Vandewalle, INSERM U478, Faculte de Medecine Xavier Bichat, BP 416, F-75870 Paris Cedex 18, France. Email: vandewal@bichat.inserm.fr 1982 Nephrol Dial Transplant (2001) 16: Editorial Comments