title: Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation.
abstract: In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus -1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P = 0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.
authors.affiliation: Transplant Institute, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Mjörnstedt
authors.forename: Søren
authors.initials: S
authors.lastname: Schwartz Sørensen
authors.forename: Bengt
authors.initials: B
authors.lastname: von Zur Mühlen
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.forename: Jesper M
authors.initials: JM
authors.lastname: Hansen
authors.forename: Claus
authors.initials: C
authors.lastname: Bistrup
authors.forename: Helene
authors.initials: H
authors.lastname: Andersson
authors.forename: Bengt
authors.initials: B
authors.lastname: Gustafsson
authors.forename: Dag
authors.initials: D
authors.lastname: Solbu
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D000068338:Everolimus; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000601:surgery* / Q000628:therapy; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus
keywords: calcineurin inhibitor; conversion; everolimus; glomerular filtration rate; kidney transplantation; long-term; renal function