Renal transplantation with expanded criteria donors: Which is the optimal immunosuppression?

Abstract

The growing gap between demand and supply for kidney transplants has led to renewed interest in the use of expanded criteria donor (ECD) kidneys in an effort to increase the donor pool. Although most studies of ECD kidney transplantation confirm lower allograft survival rates and, generally, worse outcomes than standard criteria donor kidneys, recipients of ECD kidneys generally have improved survival compared with wait-listed dialysis patients, thus encouraging the pursuit of this type of kidney transplantation. The relative benefits of transplantation using kidneys from ECDs are dependent on patient characteristics and the waiting time on dialysis. Because of the increased risk of poor graft function, calcineurin inhibitor (CNI)-induced nephrotoxicity, increased incidence of infections, cardiovascular risk, and malignancies, elderly recipients of an ECD kidney transplant are a special population that requires a tailored immunosuppressive regimen. Recipients of ECD kidneys often are excluded from transplant trials and, therefore, the optimal induction and maintenance immunosuppressive regimen for them is not known. Approaches are largely center specific and based upon expert opinion. Some data suggest that antithymocyte globulin might be the preferred induction agent for elderly recipients of ECD kidneys. Maintenance regimens that spare CNIs have been advocated, especially for older recipients of ECD kidneys. CNI-free regimens are not universally accepted due to occasionally high rejection rates. However, reduced CNI exposure and CNI-free regimens based on mammalian target of rapamycin inhibitors have shown acceptable outcomes in appropriately selected ECD transplant recipients.

Keywords: Expanded-criteria donors, Outcomes, Kidney transplantation, Immunosuppression, Survival

Core tip: Kidney donor shortage is chronic, persistent and increasing in most countries worldwide. Therefore, there has been renewed interest in the use of expanded criteria donors (ECD) to increase donor pool. Compared to standard criteria donor kidneys, ECD kidneys are associated with up to a two-fold increased risk of delayed graft function, acute rejection, and graft loss. The optimal induction and maintenance immunosuppressive regimen for ECD transplant recipients is not known due to shortage of randomized trials. Induction with antithymocyte globulin and maintenance with calcineurin inhibitors-sparing regimens have been advocated, especially for older recipients of ECD kidneys. This review provides insights into topics such as selection of appropriate candidates for kidney transplantation from ECDs, optimal management of ECD transplant recipients and discusses literature data on the immunosuppressive regimens that have been used in this patient population.