Cyclosporine Withdrawal Improves Long-Term Graft Survival in Renal Transplantation

Abstract

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.

Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

“…The primary and secondary outcomes of the study-death-censored graft survival, patient survival, and the combined end point of death or graft loss 4,5,18 -have previously been reported. Cancer outcomes were prespecified in the original trial and were briefly reported at 15 and 20 years 4,5 but were not previously analyzed and reported in detail.…”

“…Much debate has focused on the effects of the various immunosuppressive agents and dose regimens, with concerns raised about azathioprine, 4,6,7 cyclosporine, 8,9 mycophenolate mofetil, 8 tacrolimus, 10 and triple therapy. 11 Our data suggest that azathioprine-and cyclosporine-based regimens are associated with similar overall long-term cancer risks, suggesting that the risk may be mediated by the total burden of immunosuppression more than the agent.…”

“…Details of the trial, including the extent of deviations from protocol therapy, have been previously reported 4,5,18 but will be summarized in brief here.…”

“…We previously reported graft and patient survival outcomes at 15 and 20 years of median follow-up. 4,5 In this study, we compare incident cancer rates and spectrum of cancers across the three arms using the extremely prolonged follow-up provided by registry linkage, the unbiased distribution of confounders arising from the trial randomization, and extensive baseline data on cancer risk.…”

Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study

“…These efforts have focused on three possible strategies: total avoidance of CNI therapy, low-exposure CNI regimens, or CNI withdrawal (3,4). A key objective for any CNI minimization strategy is the preservation of longterm renal function, which may ultimately lead to improved graft survival but only after many years' follow-up (5). Despite the importance of long-term outcomes, however, most studies report only short-term outcomes, while data on longer follow-up periods are desperately needed.…”