title: Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study.
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).
authors: Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors: Frank
authors: F
authors: Lehner
authors: Klemens
authors: K
authors: Budde
authors: Martin
authors: M
authors: Zeier
authors: Rudolf P
authors: RP
authors: Wüthrich
authors: Petra
authors: P
authors: Reinke
authors: Ute
authors: U
authors: Eisenberger
authors: Anja
authors: A
authors: Mühlfeld
authors: Wolfgang
authors: W
authors: Arns
authors: Rolf
authors: R
authors: Stahl
authors: Katharina
authors: K
authors: Heller
authors: Oliver
authors: O
authors: Witzke
authors: Heiner H
authors: HH
authors: Wolters
authors: Barbara
authors: B
authors: Suwelack
authors: Hans Ulrich
authors: HU
authors: Klehr
authors: Manfred
authors: M
authors: Stangl
authors: Ingeborg A
authors: IA
authors: Hauser
authors: Silvio
authors: S
authors: Nadalin
authors: Martina
authors: M
authors: Porstner
authors: Christoph
authors: C
authors: May
authors: Eva-Maria
authors: EM
authors: Paulus
authors: Claudia
authors: C
authors: Sommerer
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: calcineurin inhibitors; cyclosporine; everolimus; kidney transplantation; living donor; renal function