Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy : an analysis of two randomized, multicenter trials

  • Background: Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. Methods: PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). Results: There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). Conclusions: Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. Trial registration: clinicaltrials.gov, NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT (2006-007021-32 and 2004-004346-40).

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Author:Claudia Sommerer, Oliver Witzke, Frank Lehner, Wolfgang Arns, Petra Reinke, Ute Eisenberger, Bruno Vogt, Katharina Heller, Johannes Jacobi, Markus Guba, Rolf Stahl, Ingeborg A. HauserGND, Volker Kliem, Rudolf Wüthrich, Anja Mühlfeld, Barbara Suwelack, Michael Dürr, Eva-Maria Paulus, Martin Zeier, Martina Porstner, Klemens Budde
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30231851
Parent Title (English):BMC nephrology
Publisher:BioMed Central
Place of publication:London
Contributor(s):Caroline Dunstall, Elisabeth Grünewald
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/09/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:ZEUS and HERAKLES study investigators
Release Date:2018/09/25
Tag:Diabetes; Everolimus; Kidney transplantation; PTDM; Post-transplant; TOR inhibitor
Issue:1, Art. 237
Page Number:13
First Page:1
Last Page:13
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0