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


Eisenberger, Ute; Budde, Klemens; Lehner, Frank; Sommerer, Claudia; Reinke, Petra; Witzke, Oliver; Wüthrich, Rudolf P; Stahl, Rolf; Heller, Katharina; Suwelack, Barbara; Mühlfeld, Anja; Hauser, Ingeborg A; Nadalin, Silvio; Porstner, Martina; Arns, Wolfgang; ZEUS Study Investigators (2018). Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus: an analysis from the randomized ZEUS study. BMC Nephrology, 19(1):154.

Abstract

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.

Abstract

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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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:28 June 2018
Deposited On:13 Feb 2019 13:18
Last Modified:14 Feb 2019 08:39
Publisher:BioMed Central
ISSN:1471-2369
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12882-018-0950-1
PubMed ID:29954336

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