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 5-8 ng/ml) or to continue CSA based immunosuppression (target 70-150 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<0.001). Significant effects for randomization group were evident despite short-term trough levels in the supratherapeutic range (27% (n = 26) of TAC patients at week one). Median TAC trough levels were within target range at week 4 after conversion.


CONCLUSIONS
Conversion of CSA treated kidney transplant recipients with stable graft function to TAC (target 5-8 ng/ml) showed significantly improved long-term eGFR trajectories when compared to CSA maintenance (target 70-150 ng/ml).


BACKGROUND
ClinicalTrials.gov NCT00182559 EudraCT identifier: 2004-004209-98.
Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Max
M
Plischke
Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Markus
M
Riegersperger
Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
Daniela
D
Dunkler
Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
Georg
G
Heinze
Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Željko
Ž
Kikić
Section of Nephrology, Baylor College of Medicine, Houston, Texas, United States of America.
Wolfgang C
WC
Winkelmayer
Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Gere
G
Sunder-Plassmann
D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology; D066027:Transplant Recipients
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus