Open AccessEfficacy and safety of conversion from cyclosporine to everolimus in living‐donor kidney transplant recipients: an analysis from the ZEUS study
Author(s) -
Lehner Frank,
Budde Klemens,
Zeier Martin,
Wüthrich Rudolf P.,
Reinke Petra,
Eisenberger Ute,
Mühlfeld Anja,
Arns Wolfgang,
Stahl Rolf,
Heller Katharina,
Witzke Oliver,
Wolters Heiner H.,
Suwelack Barbara,
Klehr Hans Ulrich,
Stangl Manfred,
Hauser Ingeborg A.,
Nadalin Silvio,
Porstner Martina,
May Christoph,
Paulus EvaMaria,
Sommerer Claudia
Publication year - 2014
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12411
Subject(s) - everolimus , medicine , calcineurin , urology , renal function , kidney transplantation , clinical endpoint , randomization , creatinine , adverse effect , transplantation , gastroenterology , sirolimus , acute tubular necrosis , surgery , randomized controlled trial
Summary 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)