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

Autor: Eisenberger, Ute, Budde, Klemens, Mühlfeld, Anja, Hauser, Ingeborg A., Nadalin, Silvio, Porstner, Martina, Arns, Wolfgang, ZEUS Study Investigators, Lehner, Frank, Klempnauer, Jürgen, Neumayer, Hans-H., Gerke, Peter, Klehr, Hans Ulrich, Mühlfeld, Anja Susanne, Witzke, Oliver, Pietruck, Frank, Heller, Katharina, Reinke, Petra, Senninger, Norbert, Sommerer, Claudia, Wolters, Heiner H., Suwelack, Barbara, Zeier, Martin, Stahl, Rolf, Thorban, Stefan, Stangl, Manfred, Steurer, Wolfgang, Frey, Felix, Wüthrich, Rudolf P., Clavien, Pierre-Alain
Přispěvatelé: ZEUS Study Investigators (Beitragende*r), University of Zurich, Eisenberger, Ute, Dunstall, Caroline, Grünewald, Elisabeth, ZEUS Study Investigators
Rok vydání: 2018
Předmět:
Male
Nephrology
Time Factors
mTOR inhibitor
Biopsy
medicine.medical_treatment
Medizin
030232 urology & nephrology
030230 surgery
lcsh:RC870-923
law.invention
Kidney transplantation
0302 clinical medicine
Randomized controlled trial
Medizinische Fakultät
law
2727 Nephrology
medicine.diagnostic_test
Drug Substitution
Graft Survival
Immunosuppression
Middle Aged
Cyclosporine
Female
Immunosuppressive Agents
Research Article
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Randomized
Urology
610 Medicine & health
Young Adult
03 medical and health sciences
Internal medicine
medicine
Humans
ddc:610
Everolimus
Aged
10217 Clinic for Visceral and Transplantation Surgery
business.industry
lcsh:Diseases of the genitourinary system. Urology
medicine.disease
10040 Clinic for Neurology
Transplantation
Regimen
Antibody-mediated rejection
business
Zdroj: BMC Nephrology, Vol 19, Iss 1, Pp 1-8 (2018)
BMC nephrology 19(1), 154 (2018). doi:10.1186/s12882-018-0950-1
BMC Nephrology
ISSN: 1471-2369
DOI: 10.1186/s12882-018-0950-1
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12882-018-0950-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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