PLOS One / Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function : Results from a Randomized Controlled Trial

Background Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level of GFR and offer increased statistical power. Methods Secondary analysis of a randomized controlled trial of CSA treated kidney transplant recipients with stable graft function assigned to receive 0.1 mg/kg/day TAC (target 58 ng/ml) or to continue CSA based immunosuppression (target 70150 ng/ml) at a 2:1 ratio. Renal graft function was estimated via the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) formulas. Results Forty-five patients continued CSA and 96 patients were converted to TAC with a median follow up of 24 months. Baseline demographics (except for recipient age) including native kidney disease, transplant characteristics, kidney graft function, medication use and comorbid conditions did not differ between groups. In respect to long-term renal graft function, linear mixed models showed significantly improved eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p<0.001) in the TAC versus CSA group over 24 months of follow up. Estimated eGFRCKD-EPI group differences between TAC and CSA were 3.49 (p = 0.019) at 3 months, 5.50 (p<0.001) at 12 months, and 4.48 ml/min/1.73m2 (p = 0.003) at 24 months of follow up. Baseline eGFR was a significant predictor of eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p