Cyclosporine withdrawal improves long-term graft survival in renal transplantation

Abstract

Background: The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear.

Methods: This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL).

Results: Between 1983 and 1986, 489 patients were randomized with 98% follow-up to a median of 20.6 years. Mean graft survival (censoring deaths) was superior in the WDL group (14.8 years) when compared with both AP (12.4 years, P=0.01 log-rank test) and Cy (12.5 years, P=0.01 log-rank test) groups by intention-to-treat. Without death censoring, graft survival with WDL was superior to AP (9.5 years vs. 6.7 years, P=0.04) and of borderline superiority to Cy (9.5 years vs. 8.5 years, P=0.06). Patient survival was not different between the three groups. Renal function was superior in AP (at 1, 10, and 15 years posttransplant) and WDL (at 1, 5, 10, 15, and 20 years) groups when compared with Cy.

Conclusion: This study illustrates superior long-term renal transplant survival and preservation of renal function with a protocol using cyclosporine withdrawal. If long-term renal transplant outcomes are to improve, we should reconsider guidelines recommending universal maintenance use of cyclosporine.