BMC Nephrology (Jun 2018)

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

  • Ute Eisenberger,
  • Klemens Budde,
  • Frank Lehner,
  • Claudia Sommerer,
  • Petra Reinke,
  • Oliver Witzke,
  • Rudolf P. Wüthrich,
  • Rolf Stahl,
  • Katharina Heller,
  • Barbara Suwelack,
  • Anja Mühlfeld,
  • Ingeborg A. Hauser,
  • Silvio Nadalin,
  • Martina Porstner,
  • Wolfgang Arns,
  • on behalf of the ZEUS Study Investigators

DOI
https://doi.org/10.1186/s12882-018-0950-1
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 8

Abstract

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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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