How the development of new biological agents may help minimize immunosuppression in kidney transplantation: the impact of belatacept

Abstract

The purpose of this review is to discuss the use of belatacept as part of an immunosuppression regimen in renal transplant recipients to avoid the renal and nonrenal toxicities associated with calcineurin inhibitors (CNIs). Current immunosuppression protocols utilize CNIs that are associated with renal and cardiovascular/metabolic toxicities. Belatacept, a selective costimulation blocker, is designed to provide effective immunosuppression while avoiding the toxicities associated with CNIs. Phase III trial data have demonstrated that belatacept is noninferior to cyclosporine in 1-year patient and allograft survival. Two-year data demonstrate up to a 17 ml/min/1.73 m improvement in mean measured glomerular filtration rate in belatacept-treated versus cyclosporine-treated patients. Belatacept-treated patients had better blood pressure control and lipid profiles compared to cyclosporine-treated patients. There were more cases of posttransplant lymphoproliferative disease in belatacept-treated patients, especially in Epstein-Barr virus-negative recipients or patients treated with lymphocyte-depleting agents. In a conversion trial from a CNI to belatacept, the mean increase in renal function was 7.0 and 2.1 ml/min/1.73 m in the belatacept and cyclosporine groups, respectively. Belatacept provides effective immunosuppression while avoiding or minimizing the untoward side effects seen with CNIs. Conversion from a CNI to belatacept posttransplantation appears to be safe and effective and results in improved renal allograft function. Data suggest that belatacept use may eventually lead to improved long-term allograft survival and decrease the overall long-term mortality by improving the cardiovascular and metabolic profile of renal transplant recipients.