학술논문
Five‐year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low‐exposure cyclosporine versus standard therapy
Document Type
Article
Author
Sommerer, Claudia; Duerr, Michael; Witzke, Oliver; Lehner, Frank; Arns, Wolfgang; Kliem, Volker; Ackermann, Daniel; Guba, Markus; Jacobi, Johannes; Hauser, Ingeborg A.; Stahl, Rolf; Reinke, Petra; Rath, Thomas; Veit, Justyna; Mehrabi, Arianeb; Porstner, Martina; Budde, Klemens; Mühlfeld, Anja; Babel, Nina; Schäffner, Elke; Hugo, Christian; Pressmar, Katharina; Pietruck, Frank; Kribben, Andreas; Asbe‐Vollkopf, Aida; Pisarski, Przemyslaw; Drognitz, Oliver; Thaiss, Friedrich; Klempnauer, Jürgen; Weithofer, Peter; Zeier, Martin; Huppertz, Andrea; Hackenberg, Ruth; Nitschke, Martin; Jauch, Karl‐Günter; Andrassy, Joachim; Stangl, Manfred; Thorban, Stefan; Banas, Bernhard; Frey, Felix; Vogt, Bruno
Source
American Journal of Transplantation; December 2018, Vol. 18 Issue: 12 p2965-2976, 12p
Subject
Language
ISSN
16006135; 16006143
Abstract
HERAKLESwas a 1‐year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine‐based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low‐exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4‐year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard‐CNI,CNI‐free and low‐CNIgroups, respectively. Adjusted estimated GFRat year 5 was significantly higher in the CNI‐free group versus standard CNI(difference 7.2 mL/min/1.73 m2, P< .001) or low CNI(difference 7.6 mL/min/1.73 m2, P< .001). For patients who continued randomized therapy for 5 years, differences were 14.4 mL/min/1.73 m2and 10.1 mL/min/1.73 m2, respectively. Biopsy‐proven acute rejection occurred during the 4‐year extension study in 7.6%, 8.6%, and 9.0% of patients in the standard‐CNI,CNI‐free and low‐CNIgroups, respectively (P= .927). In conclusion, conversion to a CNI‐free everolimus regimen 3 months after kidney transplantation improved long‐term graft function, particularly in patients who continued the CNI‐free regimen. Low CNIwith everolimus did not improve renal function. Efficacy was comparable between groups but frequent immunosuppression changes should be taken into account. Five‐year follow‐up data from patients randomized at three months after kidney transplantation to receive standard calcineurin inhibitor (CNI) therapy, everolimus‐based CNI‐free therapy, or everolimus with low‐exposure CNI show that early CNI withdrawal maintains better long‐term renal function without an increase in biopsy‐proven acute rejection, with a similar rate of infections and a low rate of discontinuations due to adverse events in all three treatment groups.