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Efficacy and safety of conversion from cyclosporine to everolimus in living‐donor kidney transplant recipients: an analysis from the ZEUS study |
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| Authors: | Frank Lehner Klemens Budde Martin Zeier Rudolf P. Wüthrich Petra Reinke Ute Eisenberger Anja Mühlfeld Wolfgang Arns Rolf Stahl Katharina Heller Oliver Witzke Heiner H. Wolters Barbara Suwelack Hans Ulrich Klehr Manfred Stangl Ingeborg A. Hauser Silvio Nadalin Martina Porstner Christoph May Eva‐Maria Paulus Claudia Sommerer the ZEUS Study Investigators |
| Affiliation: | 1. Department of General, Visceral and Transplantation Surgery, Hannover Medical School, , Hannover, Germany;2. Department of Nephrology, Charité Universit?tsmedizin Berlin, , Berlin, Germany;3. Department of Nephrology, University Hospital Heidelberg, , Heidelberg, Germany;4. Division of Nephrology, University Hospital, , Zürich, Switzerland;5. Department of Nephrology and Hypertension, University of Bern, Inselspital, , Bern, Switzerland;6. Division of Nephrology and Immunology, University Hospital of the RWTH Aachen, , Aachen, Germany;7. Transplant Center Cologne, Cologne General Hospital, , Cologne, Germany;8. Division of Nephrology, University Medical Center Hamburg‐Eppendorf, , Hamburg, Germany;9. Division of Nephrology, Department of Medicine, University of Erlangen, , Erlangen, Germany;10. Department of Nephrology, University Hospital Essen, University of Duisburg‐Essen, , Essen, Germany;11. Department of General Surgery, University of Münster, , Münster, Germany;12. Department of Internal Medicine D, Division of Nephrology, University of Münster, , Münster, Germany;13. Department of Nephrology, University Hospital of Bonn, , Bonn, Germany;14. Department of Transplant Surgery, LMU Munich, , Munich, Germany;15. Department of Nephrology, University Hospital Frankfurt, Goethe‐University Frankfurt, , Frankfurt am Main, Germany;16. Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, , Tübingen, Germany;17. Novartis Pharma, , Novartis Pharma, Nuremberg, Germany |
| Abstract: | Conversion of living‐donor kidney transplant patients from calcineurin inhibitor therapy to an mTOR inhibitor is poorly documented. In the prospective, multicentre ZEUS study, 300 kidney transplant recipients without prior rejection (Banff grade >1) and serum creatinine ≤265 μmol/l were randomized to continue cyclosporine or convert to everolimus at 4.5 months post‐transplant. In a post hoc analysis of 80 living‐donor recipients, adjusted estimated GFR (Nankivell) at month 12 (the primary endpoint) was 74.3 (95% CI [70.7, 77.9]) ml/min/1.73 m2 with everolimus versus 63.8 (95% CI [60.0, 67.7]) ml/min/1.73 m2) with cyclosporine, a difference of 10.5 ml/min/1.73 m2 in favour of everolimus (P < 0.001). From randomization to month 12, adjusted estimated GFR increased by a mean of 9.8 (95% CI [6.2, 13.4]) ml/min/1.73 m2 with everolimus versus ?0.7 (95% CI [?4.6, 3.1]) ml/min/1.73 m2) (P < 0.001) with cyclosporine. There were six biopsy‐proven acute rejection episodes in everolimus‐treated patients (five Banff grade I) and one episode in cyclosporine‐treated patients (Banff grade 1). Overall safety profile was similar between groups. Discontinuation due to adverse events occurred in three everolimus patients (7.1%) and five cyclosporine patients (13.2%) between randomization and month 12. Initiation of everolimus with early elimination of calcineurin therapy is associated with a significant renal benefit at 12 months post‐transplant that is observed in both living and deceased‐donor recipients. (clinicaltrials.gov NCT00154310) |
| Keywords: | calcineurin inhibitors cyclosporine everolimus kidney transplantation living donor renal function |