Influence of Immunosuppressive Regimens on Graft Survival and Secondary Outcomes After Kidney Transplantation

Abstract

There have been striking changes during the last 10 years concerning the choice of calcineurin inhibitor and antimetabolite agent prescribed after kidney transplantation. A retrospective analysis of 51,303 patients undergoing deceased-donor kidney transplantation during 1998 to 2007 was performed using multivariate regression analysis. All patients received cyclosporine A (CsA) or tacrolimus (Tac) with azathioprine (AZA) or mycophenolic acid (MPA) on an intention-to-treat basis with corticosteroids plus/minus antibody induction. Graft survival rates and secondary outcomes were analyzed. A subanalysis was performed for transplants undertaken during 2002 to 2007, in which all patients were treated with MPA plus corticosteroids and CsA or Tac. All-cause graft failure and death-censored graft failure to 5 years posttransplant did not differ significantly between Tac and CsA. We found no evidence in support of previous claims that MPA results in superior long-term graft survival compared with AZA treatment. At the end of year 1, Tac was associated with a lower risk for serum creatinine more than or equal to 130 mumol/L (P<0.001) and hypercholesterolemia (P<0.001) versus CsA, but a higher risk for de novo posttransplant diabetes (P<0.001). MPA treatment was associated with a lower risk of acute rejection (P<0.001) but a higher risk of hospitalization because of infection (P<0.001) versus AZA. Five-year graft survival in deceased-donor kidney transplant recipients is equivalent in patients receiving CsA- or Tac-based immunosuppression, and in those receiving MPA or AZA. The absence of a survival benefit with modern agents is relevant in the current cost-conscious era of prescribing.