TY  - JOUR
A1  - Eisenberger, Ute
A1  - Budde, Klemens
A1  - Lehner, Frank
A1  - Sommerer, Claudia
A1  - Reinke, Petra
A1  - Witzke, Oliver
A1  - Wüthrich, Rudolf
A1  - Stahl, Rolf
A1  - Heller, Katharina
A1  - Suwelack, Barbara
A1  - Mühlfeld, Anja
A1  - Hauser, Ingeborg A.
A1  - Nadalin, Silvio
A1  - Porstner, Martina
A1  - Arns, Wolfgang
T1  - Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus : an analysis from the randomized ZEUS study
T2  - BMC nephrology
N2  - 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.
KW  - Everolimus
KW  - mTOR inhibitor
KW  - Biopsy
KW  - Kidney transplantation
KW  - Randomized
KW  - Antibody-mediated rejection
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46928
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-469283
SN  - 1471-2369
N1  - 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.
VL  - 19
IS  - 1, Art. 154
SP  - 1
EP  - 8
PB  - BioMed Central
CY  - London
ER  -