title: Five-year outcomes in kidney transplant patients converted from cyclosporine to everolimus: the randomized ZEUS study.
abstract: ZEUS study was an open-label, 12-month, multicenter study in which 300 de novo kidney transplant recipients were randomized to continue receiving cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant. Five-year follow-up data were available for 245/269 patients (91.1%) who completed the core 12-month study (123 everolimus, 109 CsA). At 5 years, adjusted estimated GFR was 66.2 mL/min/1.73 m(2) with everolimus versus 60.9 mL/min/1.73 m(2) with CsA; the mean difference was 5.3 mL/min/1.73 m(2) in favor of everolimus (95% CI 2.4, 8.3; p < 0.001 [intent-to-treat population]). In a post hoc analysis of patients remaining on study drug at 5 years (everolimus 77, CsA 86), mean difference was 8.2 mL/min/1.73 m(2) (95% CI 4.3, 12.1; p < 0.001) in favor of everolimus. The cumulative incidence of biopsy-proven acute rejection postrandomization was 13.6% with everolimus versus 7.5% with CsA (p = 0.095), largely accounted for by grade I rejection (16/21 patients and 7/11 patients, respectively). Postrandomization, graft loss, mortality, serious adverse events and neoplasms were similar in both arms. In conclusion, conversion of kidney transplant patients to everolimus at 4.5 months posttransplant is associated with a significant improvement in renal function that is maintained to at least 5 years. The increase in early mild acute rejection did not affect long-term graft function.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Budde
authors.forename: F
authors.initials: F
authors.lastname: Lehner
authors.forename: C
authors.initials: C
authors.lastname: Sommerer
authors.forename: P
authors.initials: P
authors.lastname: Reinke
authors.forename: W
authors.initials: W
authors.lastname: Arns
authors.forename: U
authors.initials: U
authors.lastname: Eisenberger
authors.forename: R P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: A
authors.initials: A
authors.lastname: Mühlfeld
authors.forename: K
authors.initials: K
authors.lastname: Heller
authors.forename: M
authors.initials: M
authors.lastname: Porstner
authors.forename: J
authors.initials: J
authors.lastname: Veit
authors.forename: E-M
authors.initials: EM
authors.lastname: Paulus
authors.forename: O
authors.initials: O
authors.lastname: Witzke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012107:Research Design; D012307:Risk Factors; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus
keywords: Clinical research; immunosuppressant; kidney transplantation; mechanistic target of rapamycin (mTOR); mechanistic target of rapamycin: everolimus; nephrology; practice