Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials
Abstract Background Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) o...
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| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Nephrology |
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| Online Access: | http://link.springer.com/article/10.1186/s12882-018-1031-1 |
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| author | Claudia Sommerer Oliver Witzke Frank Lehner Wolfgang Arns Petra Reinke Ute Eisenberger Bruno Vogt Katharina Heller Johannes Jacobi Markus Guba Rolf Stahl Ingeborg A. Hauser Volker Kliem Rudolf P. Wüthrich Anja Mühlfeld Barbara Suwelack Michael Duerr Eva-Maria Paulus Martin Zeier Martina Porstner Klemens Budde on behalf of the ZEUS and HERAKLES study investigators |
| author_facet | Claudia Sommerer Oliver Witzke Frank Lehner Wolfgang Arns Petra Reinke Ute Eisenberger Bruno Vogt Katharina Heller Johannes Jacobi Markus Guba Rolf Stahl Ingeborg A. Hauser Volker Kliem Rudolf P. Wüthrich Anja Mühlfeld Barbara Suwelack Michael Duerr Eva-Maria Paulus Martin Zeier Martina Porstner Klemens Budde on behalf of the ZEUS and HERAKLES study investigators |
| author_sort | Claudia Sommerer |
| collection | DOAJ |
| description | Abstract Background Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. Methods PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). Results There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). Conclusions Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. Trial registration clinicaltrials.gov, NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT (2006-007021-32 and 2004-004346-40). |
| first_indexed | 2024-12-11T20:28:25Z |
| format | Article |
| id | doaj.art-03ee2b06a3cf4b8ba50f0091731a8e25 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-11T20:28:25Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-03ee2b06a3cf4b8ba50f0091731a8e252022-12-22T00:51:53ZengBMCBMC Nephrology1471-23692018-09-0119111310.1186/s12882-018-1031-1Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trialsClaudia Sommerer0Oliver Witzke1Frank Lehner2Wolfgang Arns3Petra Reinke4Ute Eisenberger5Bruno Vogt6Katharina Heller7Johannes Jacobi8Markus Guba9Rolf Stahl10Ingeborg A. Hauser11Volker Kliem12Rudolf P. Wüthrich13Anja Mühlfeld14Barbara Suwelack15Michael Duerr16Eva-Maria Paulus17Martin Zeier18Martina Porstner19Klemens Budde20on behalf of the ZEUS and HERAKLES study investigatorsDepartment of Nephrology, University of HeidelbergDepartment of Infectious Diseases, University Duisburg-EssenDepartment of General, Visceral and Transplantation Surgery, Hannover Medical SchoolDepartment of Nephrology and Transplantation, Cologne Merheim Medical CenterDepartment of Nephrology and Intensive Care, Charité Campus Virchow, Charité-Universitätsmedizin BerlinDepartment of Nephrology and Hypertension, University of Bern, InselspitalDepartment of Nephrology and Hypertension, University of Bern, InselspitalDepartment of Nephrology and Hypertension, University of Erlangen-NurembergDepartment of Nephrology and Hypertension, University of Erlangen-NurembergDepartment of General-, Visceral- and Transplantation Surgery, Munich University HospitalDivision of Nephrology, University Medical Center Hamburg-EppendorfMed. Klinik III, Department of Nephrology, UKF, Goethe UniversityDepartment of Internal Medicine and Nephrology, Kidney Transplant Center, Nephrological Center of Lower Saxony, Klinikum HannDivision of Nephrology, University HospitalDivision of Nephrology and Immunology, University Hospital RWTH AachenDepartment of Internal Medicine - Transplant Nephrology, University Hospital of MünsterDepartment of Nephrology, Charité Universitätsmedizin BerlinNovartis Pharma GmbHDepartment of Nephrology, University of HeidelbergNovartis Pharma GmbHDepartment of Nephrology, Charité Universitätsmedizin BerlinAbstract Background Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. Methods PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). Results There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). Conclusions Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. Trial registration clinicaltrials.gov, NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT (2006-007021-32 and 2004-004346-40).http://link.springer.com/article/10.1186/s12882-018-1031-1DiabetesEverolimusKidney transplantationTOR inhibitorPTDMPost-transplant |
| spellingShingle | Claudia Sommerer Oliver Witzke Frank Lehner Wolfgang Arns Petra Reinke Ute Eisenberger Bruno Vogt Katharina Heller Johannes Jacobi Markus Guba Rolf Stahl Ingeborg A. Hauser Volker Kliem Rudolf P. Wüthrich Anja Mühlfeld Barbara Suwelack Michael Duerr Eva-Maria Paulus Martin Zeier Martina Porstner Klemens Budde on behalf of the ZEUS and HERAKLES study investigators Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials BMC Nephrology Diabetes Everolimus Kidney transplantation TOR inhibitor PTDM Post-transplant |
| title | Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials |
| title_full | Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials |
| title_fullStr | Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials |
| title_full_unstemmed | Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials |
| title_short | Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials |
| title_sort | onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy an analysis of two randomized multicenter trials |
| topic | Diabetes Everolimus Kidney transplantation TOR inhibitor PTDM Post-transplant |
| url | http://link.springer.com/article/10.1186/s12882-018-1031-1 |
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