Five-year outcomes in kidney transplant patients converted from cyclosporine to everolimus: the randomized ZEUS study.

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.