title: Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial.
abstract: In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n = 359) or remain on standard calcineurin inhibitor (CNI) therapy (n = 356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.732versus -1.5(1.5) mL/min/1.732(p = 0.116). Biopsy-proven acute rejection (BPAR) at month 12 was more frequent under everolimus versus CNI overall (9.7% vs. 4.8%, p = 0.014) and versus tacrolimus-treated patients (2.6%, p < 0.001) but similar to cyclosporine-treated patients (8.8%, p = 0.755). Reporting on de novo donor-specific antibodies (DSA) was limited but suggested more frequent anti-HLA Class I DSA under everolimus. Change in left ventricular mass index was similar. Discontinuation due to adverse events was more frequent with everolimus (23.6%) versus CNI (8.4%). In conclusion, conversion to everolimus at 10-14 weeks posttransplant was associated with renal function similar to that with standard therapy overall. Rates of BPAR were low in all groups, but lower with tacrolimus than everolimus.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Section of Nephrology, Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Holdaas
authors.affiliation: Section of Transplant Surgery, Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Øyen
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: J-S
authors.initials: JS
authors.lastname: Sanders
authors.affiliation: Department of Nephrology, Columbia Asia Hospitals, Malleshwaram West, Bangalore, India.
authors.forename: S
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Bemelman
authors.affiliation: Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sommerer
authors.affiliation: Department of Nephrology, Hospital del Mar, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Faculty of Medicine, Chulalongkorn University and Excellent Center of Organ Transplantation, King Chulalongkorn Memorial Hospital, Patumwan, Bangkok, Thailand.
authors.forename: Y
authors.initials: Y
authors.lastname: Avihingsanon
authors.affiliation: Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: C
authors.initials: C
authors.lastname: Pongskul
authors.affiliation: Department of Nephrology and Kidney Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Oppenheimer
authors.affiliation: Kidney, Liver and Pancreas Transplant Unit, CRAI Norte, Ministry of Health, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Toselli
authors.affiliation: University of Adelaide and Central and Northern Adelaide Renal and Transplant Service, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Russ
authors.affiliation: Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, NJ.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Research and Development, Novartis Pharma AG, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Research and Development, Novartis Pharma AG, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kochuparampil
authors.affiliation: Department of Nephrology, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Department of Nephrology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: van der Giet
mesh_terms: D000068338:Everolimus / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D016559:Tacrolimus
keywords: calcineurin inhibitor (CNI); cardiovascular disease; clinical research/practice; clinical trial; immunosuppressant; immunosuppression/immune modulation; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; mechanistic target of rapamycin: everolimus