Long-term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after.

Abstract

Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal. This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3months postgraft. At 10years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI-related toxicity (P=.019) and moderate-to-severe IF/TA (P=.004) were higher in the CsA group. Ten-year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI [5.05-26.79], P<.0001). MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.