Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus : an analysis from the randomized ZEUS study

  • Background: Conversion from calcineurin inhibitor (CNI) therapy to everolimus within 6 months after kidney transplantation improves long-term graft function but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR). We performed a post-hoc analysis of histological data from a randomized trial in order to further analyze histologic information obtained from indication and protocol biopsies up to 5 years after transplantation. Methods: Biopsy samples obtained up to 5 years post-transplant were analyzed from the randomized ZEUS study, in which kidney transplant patients were randomized at month 4.5 to switch to everolimus (n = 154) or remain on cyclosporine (CsA)-based immunosuppression (n = 146). All patients received mycophenolate and steroids. Results: At least one investigator-initiated biopsy was undertaken in 53 patients in each group between randomization and year 5, with a mean (SD) of 2.6 (1.7) and 2.2 (1.4) biopsies per patient in the everolimus and CsA groups, respectively. In the everolimus and CsA groups, investigator-initiated biopsies showed (i) BPAR in 12.3 and 7.5% (p = 0.182) of patients, respectively, with episodes graded mild in 22/24 and 18/20 cases (ii) CsA toxicity lesions in 4.5 and 10.3% of patients (p = 0.076) (iii) antibody-mediated rejection in 0.6 and 2.7% of patients (p = 0.204), respectively. Conclusions: This analysis of histological findings in the ZEUS study to 5 years after kidney transplantation shows no increase in antibody-mediated rejection under everolimus-based therapy with a lower rate of CNI-related toxicity compared to a conventional CsA-based regimen, and confirms the preponderance of mild BPAR seen in the main study after the early switch to CsA-free everolimus therapy. Trial registration: ClinicalTrials.gov NCT00154310. Date of registration: September 12, 2005.

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Author:Ute Eisenberger, Klemens Budde, Frank Lehner, Claudia Sommerer, Petra Reinke, Oliver Witzke, Rudolf Wüthrich, Rolf Stahl, Katharina Heller, Barbara Suwelack, Anja Mühlfeld, Ingeborg A. Hauser, Silvio Nadalin, Martina Porstner, Wolfgang Arns
URN:urn:nbn:de:hebis:30:3-469283
DOI:https://doi.org/10.1186/s12882-018-0950-1
ISSN:1471-2369
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29954336
Parent Title (English):BMC nephrology
Publisher:BioMed Central
Place of publication:London
Contributor(s):Caroline Dunstall, Elisabeth Grünewald
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/06/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:ZEUS Study Investigators
Release Date:2018/07/03
Tag:Antibody-mediated rejection; Biopsy; Everolimus; Kidney transplantation; Randomized; mTOR inhibitor
Volume:19
Issue:1, Art. 154
Page Number:8
First Page:1
Last Page:8
Note:
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.
HeBIS-PPN:435983415
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0