Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study
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, ZEUS Study Investigators, 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, ZEUS Study Investigators
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 m(2) with everolimus versus 63.8 (95% CI [60.0, 67.7]) ml/min/1.73 m(2) ) with cyclosporine, a difference of 10.5 ml/min/1.73 m(2) 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 m(2) with everolimus versus -0.7 (95% CI [-4.6, 3.1]) ml/min/1.73 m(2) ) (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.
© 2014 Steunstichting ESOT.
Source: PubMed