title: Early conversion from cyclosporine to everolimus following living-donor kidney transplantation: outcomes at 5 years posttransplant in the randomized ZEUS trial.
abstract: OBJECTIVE
  To assess 5-year efficacy, renal, and safety outcomes following early conversion from cyclosporine to everolimus vs. a standard cyclosporine-based regimen in living-donor kidney transplant (LDKT) recipients.
  
  
  METHODS
  The ZEUS study was a randomized, open-label, 1-year, multicenter study in which 300 de novo kidney transplant recipients continued to receive cyclosporine or converted to everolimus at 4.5 months post-transplant, with annual follow-up visits to 5 years post-transplant.
  
  
  RESULTS
  Of the 80 LDKT patients who were randomized, 75 completed the 1-year core study and 60 attended the 5-year follow-up visit. At year 5, 15/31 (48.4%) everolimus patients and 20/29 (69.0%) cyclosporine patients remained on the study drug. Mean adjusted estimated glomerular filtration rate (GFR) at year 5 in LDKT recipients was 67.2 vs. 60.8 mL/min/1.73m2 for everolimus vs. cyclosporine (mean difference 6.4 mL/min/1.73m2; p = 0.031). For patients who remained on study drug, the mean difference was 13.2 mL/min/1.73m2 (p = 0.003), but no significant difference was seen in patients who switched from study drug (mean -2.6 mL/min/1.73m2, p = 0.701). Patient and graft survival rates were similar with everolimus and cyclosporine. Biopsy-proven acute rejection occurred in 22.0% vs. 7.5% of LDKT patients randomized to everolimus vs. cyclosporine (p = 0.116). Only 1 LDKT patient discontinued everolimus due to adverse events during years 1 - 5.
  
  
  CONCLUSIONS
  Early initiation of everolimus with calcineurin-inhibitor (CNI) withdrawal after LDKT improved graft function to 5 years post-transplant compared to standard CNI-based therapy. The renal benefit was concentrated in patients who remained on everolimus. An increase in mild acute rejection was not associated with long-term graft loss.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Ute
authors.initials: U
authors.lastname: Eisenberger
authors.forename: Anja
authors.initials: A
authors.lastname: Mühlfeld
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahl
authors.forename: Katharina
authors.initials: K
authors.lastname: Heller
authors.forename: Heiner H
authors.initials: HH
authors.lastname: Wolters
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Klehr
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Hauser
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangl
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.forename: Michael
authors.initials: M
authors.lastname: Dürr
authors.forename: Martina
authors.initials: M
authors.lastname: Porstner
authors.forename: Christoph
authors.initials: C
authors.lastname: May
authors.forename: Peter
authors.initials: P
authors.lastname: Wimmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000175:diagnosis; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus