Mechanisms of chronic allograft dysfunction.
This review was designed to highlight new findings that have contributed to our knowledge of the pathogenesis of late graft dysfunction. Both immune and nonimmune causes contribute to its development. Specific contributors to late graft dysfunction have been recently recognized and are potential targets for new treatment options. The variables associated with late graft failure include donor age and tissue quality, brain death and other issues specific to the deceased donor, tissue injury secondary to organ preservation, alloimmune-mediated injury, and posttransplantation factors in the recipient, such as viral infections, hypertension, drug toxicity, and hyperlipidemia. One of the critical variables that is controllable is the total ischemic time; the longer the ischemic episode, the worse the long-term results of the transplant are. Another significant obstacle to long-term allograft survival is the MHC barrier. The roles of B cells and alloantibody as effectors of alloimmunity have been underestimated; emerging studies strongly suggest that previous sensitization and/or de novo donor-anti-human lymphocyte antigen (HLA) antibodies secondary to poor HLA matching portend a poor prognosis for allograft survival, even in the presence of chronic T-cell-specific immunosuppression.