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

• Main Authors: 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
• Format: Article
• Language: English
• Published: BMC 2018-06-01
• Series: BMC Nephrology
• Subjects: Everolimus; mTOR inhibitor; Biopsy; Kidney transplantation; Randomized; Antibody-mediated rejection
• Online Access: http://link.springer.com/article/10.1186/s12882-018-0950-1

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.