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/1.73 2 versus - 1.5(1.5) mL/min/1.73(2) (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.

de Fijter, J.w., Holdaas, H., Oyen, O., Sanders, J.-., Sundar, S., Bemelman, F.j., et al. (2017). Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial. AMERICAN JOURNAL OF TRANSPLANTATION, 17(7), 1853-1867 [10.1111/ajt.14186].

Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial

Russ G.;Tisone G.;
2017-01-01

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/1.73 2 versus - 1.5(1.5) mL/min/1.73(2) (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.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18 - CHIRURGIA GENERALE
English
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; Everolimus; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Risk Factors; Tacrolimus
de Fijter, J.w., Holdaas, H., Oyen, O., Sanders, J.-., Sundar, S., Bemelman, F.j., et al. (2017). Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial. AMERICAN JOURNAL OF TRANSPLANTATION, 17(7), 1853-1867 [10.1111/ajt.14186].
de Fijter, Jw; Holdaas, H; Oyen, O; Sanders, J-; Sundar, S; Bemelman, Fj; Sommerer, C; Pascual, J; Avihingsanon, Y; Pongskul, C; Oppenheimer, F; Toselli, L; Russ, G; Wang, Z; Lopez, P; Kochuparampil, J; Cruzado, Jm; van der Giet, M; Gaite, Le; Lopez, Vf; Maldonado, R; Massari, P; Novoa, P; Palti, G; Chadban, S; Kanellis, J; Masterson, R; Oberbauer, R; Saemann, M; Kuypers, D; Lohmus, A; Cassuto, E; Frimat, L; Lebranchu, Y; Le Meur, Y; Rostaing, L; Hauser, A; Muehlfeld, A; Nashan, B; Suwelack, B; Weithofer, P; Witzke, O; Zeier, M; Apostolou, T; Boletis, I; Gourmenos, D; Jasuja, S; Khullar, D; Ravishankar, Ms; Sharma, Rk; Garosi, G; Rigotti, P; Tisone, G; Todeschini, P; Acevedo, R; Rozentais, R; Juarez, Fj; Mier, Gm; Urrea, M; Machado, D; Nolasco, F; Sampaio, S; Dubanova, A; Lucan, M; Kolsanov, Av; Medvedev, Vl; Moysyuk, Yg; Nesterenko, V; Perlin, Dv; Ulyankina, Iv; Zagainov, E; Dalmau, A; Hernandez, D; Millan, S; Avhingsanon, Y; Turkmen, A; Tuncer, M; Yildiz, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/241573
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