1. Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial
- Author
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de Fijter, J. W., Holdaas, H., Oyen, O., Sanders, J. -S., Sundar, S., Bemelman, F. J., Sommerer, C., Pascual, J., Avihingsanon, Y., Pongskul, C., Oppenheimer, F., Toselli, L., Russ, G., Wang, Z., Lopez, P., Kochuparampil, J., Cruzado, J. M., van der Giet, M., Gaite, L. E., Lopez, V. F., 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, M. S., Sharma, R. K., Garosi, G., Rigotti, P., Tisone, G., Todeschini, P., Acevedo, R., Rozentais, R., Juarez, F. J., Mier, G. M., Urrea, M., Machado, D., Nolasco, F., Sampaio, S., Dubanova, A., Lucan, M., Kolsanov, A. V., Medvedev, V. L., Moysyuk, Y. G., Nesterenko, V., Perlin, D. V., Ulyankina, I. V., Zagainov, E., Dalmau, A., Hernandez, D., Millan, S., Avhingsanon, Y., Turkmen, A., Tuncer, M., Yildiz, A., DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, Kuypers, Dirk, AII - Inflammatory diseases, Nephrology, AII - Amsterdam institute for Infection and Immunity, Groningen Kidney Center (GKC), and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
Graft Rejection ,Male ,HLA ANTIBODIES ,immunosuppressant ,kidney transplantation/nephrology ,ELEVATE study ,SIROLIMUS ,immunosuppression/immune modulation ,030204 cardiovascular system & hematology ,030230 surgery ,Pharmacology ,Kidney Function Tests ,Kidney Failure ,0302 clinical medicine ,Postoperative Complications ,cardiovascular disease ,Risk Factors ,Clinical endpoint ,Immunology and Allergy ,DONOR-SPECIFIC ANTIBODIES ,Pharmacology (medical) ,Chronic ,CARDIAC-HYPERTROPHY ,Kidney transplantation ,calcineurin inhibitor (CNI) ,clinical research/practice ,clinical trial ,kidney (allograft) function/dysfunction ,mechanistic target of rapamycin: everolimus ,Everolimus ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Graft Survival ,Humans ,Immunosuppressive Agents ,Kidney Failure, Chronic ,Kidney Transplantation ,Middle Aged ,Prognosis ,Tacrolimus ,RENAL-TRANSPLANTATION ,Kidney transplant, ELEVATE study, Certican ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,Certican ,Urology ,Renal function ,Mycophenolic acid ,03 medical and health sciences ,LEFT-VENTRICULAR MASS ,PRESSURE-OVERLOAD ,medicine ,Kidney transplant ,Transplantation ,Science & Technology ,business.industry ,medicine.disease ,Settore MED/18 ,Calcineurin ,RECIPIENTS ,MAMMALIAN TARGET ,Sirolimus ,CYCLOSPORINE ,Surgery ,business - Abstract
none 24 si 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/1.732 versus -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 open de Fijter JW, Holdaas H, Øyen O, Sanders JS, 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; ELEVATE Study Group: [...; Guido Garosi; Paolo Rigotti; Giuseppe Tisone; Paola Todeschini; ...] de Fijter JW, Holdaas H, Øyen O, Sanders JS, 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; ELEVATE Study Group: [..; Guido Garosi; Paolo Rigotti; Giuseppe Tisone; Paola Todeschini; ..]
- Published
- 2017