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