Chronic allograft failure: the clinical problem.

Long-term survival statistics for organ allografts have not improved substantially over time, despite improved immunosuppression and organ preservation and better surgical and perioperative management. Chronic rejection is the most important long-term limitation in allografts and increasingly seems to be caused by a multifactorial series of antigen-dependent and antigen-independent factors. Early injury is critical to late events, whether antigen driven (early acute rejection episodes and human leukocyte antigen mismatching) or antigen independent (ischemia/reperfusion injury and brain death). Ongoing alloimmunologic injury to the host and inadequate organ mass functioning (donor age, gender, race, and organ size) also seem to be important to this persisting process. Associated recipient conditions, which includes hypertension and hyperlipidemia, and postoperative complications, which include drug nephrotoxicity and infections, may affect this late-phase graft loss. These deleterious risk factors for chronic rejection of long-functioning allografts are an important subject for future investigation.