CYCLOSPORINE WITHDRAWAL IN RENAL TRANSPLANT RECIPIENTS

Abstract

12 In randomized controlled trials, elective Cyclosporine A (CsA) withdrawal(WDL) has not affected short-term graft survival. We retrospectively compared late, conditional graft survival (CGS), i.e., conditional on survival at 1 year, in 751 consecutive patients transplanted between 1/1/85 and 12/31/96 who had: 1) conventional immunosuppression without CsA (n=177, 24%), 2) elective CsA WDL after 1 year (n=394, 52%), 3) elective continuation of CsA) at the request of the patient or private nephrologist (n=107, 14%), 4) CsA WDL due to failure or toxicity of CsA (n=29, 4%), or 5) CsA continuation because of rejection or intolerance to azathioprine (n=44, 6%). All patients received prednisone and, if possible, azathioprine. The 3- and 6-year (Kaplan Meier) CGS were very low in groups 4 (68% and 37%) and 5 (59% and 37%), illustrating the potential fallacy of using registry data that includes patients with non-elective CsA WDL or non-elective CsA continuation to judge the effects of elective CsA WDL on CGS. The 3- and 6-year CGS in groups 1, 2 and 3, respectively, were: 87% and 76% (n=145 and 100), 94% and 76% (n=313 and 161), and 95% and 87% (n=67 and 26), p=0.16 by Log Rank. After adjusting for differences in multiple risk factors in a Cox proportional hazards model, there was a trend for reduced CGS with conventional immunosuppression without CsA (p=0.062), and a trend for reduced CGS with elective CsA WDL (p=0.065). The cumulative incidence of acute rejection between 1 and 6 years post-transplant was 28%, 28%, and 13% in groups 1, 2 and 3, respectively(p=0.014). Nevertheless, according to the 1997 UNOS Center Specific Report for kidney transplants from 1/1/88 through 4/30/92, 3-year CGS was 88.1% at our center, which was comparable to the expected (adjusted) 87.6% 3-year CGS. We conclude that the use of CsA vs. conventional immunosuppression, and elective CsA WDL, have had either no effect or a small effect (p>0.05) on late graft failure at out center. The rate of late acute rejection is the same after CsA WDL as it was before the introduction of CsA, challenging the notion that WDL actually causes acute rejection. A trend (p>0.05) toward improved CGS among patients who elected to continue CsA may be due to chance, may be the result of selection bias, or may be due to improved CGS from continued CsA(suggesting the need for additional long-term follow-up). We speculate that newer adjunctive immunosuppression may reduce the incidence of acute rejection after CsA WDL and enhance long-term CGS in the future.