A Randomized,Controlled Study to Assess the Conversion From Calcineurin‐Inhibitors to Everolimus After Liver Transplantation—PROTECT |
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| Authors: | L. Fischer J. Klempnauer S. Beckebaum H. J. Metselaar P. Neuhaus P. Schemmer U. Settmacher N. Heyne P‐A. Clavien F. Muehlbacher I. Morard H. Wolters W. Vogel T. Becker M. Sterneck F. Lehner C. Klein G. Kazemier A. Pascher J. Schmidt F. Rauchfuss A. Schnitzbauer S. Nadalin M. Hack S. Ladenburger H. J. Schlitt |
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| Affiliation: | 1. University Medical Center Hamburg‐Eppendorf, Department of Hepatobiliary and Transplant Surgery, Hamburg, Germany;2. Hannover Medical School (MHH), Clinic for General, Abdominal and Transplant Surgery, Hannover, Germany;3. Essen University Hospital, Department of General, Visceral and Transplantation Surgery, Essen, Germany;4. Erasmus MC, University Hospital Rotterdam, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands;5. Charité University Medical Center Berlin, Clinic for General, Abdominal and Transplant Surgery, Berlin, Germany;6. University Hospital Heidelberg, Department of General, Visceral and Transplant Surgery, Heidelberg, Germany;7. Jena University Hospital, Department of General, Abdominal and Vascular Surgery, Jena, Germany;8. University Hospital Tuebingen, Department of General, Visceral and Transplant Surgery, Tuebingen, Germany;9. University of Zurich, Swiss HPB and Transplantation Center, Department of Surgery, Zurich, Switzerland;10. Medical University of Vienna, Surgical Clinic, Division of Transplant Surgery, Vienna, Austria;11. H?pitaux Universitaires de Genève (HUG), Gastroentérologie et Hépatologie, Genève, Switzerland;12. Muenster University Hospital, Clinic and Policlinic for General Surgery, Muenster, Germany;13. Innsbruck Medical University, Department of Internal Medicine II (Gastroenterology and Hepatology), Innsbruck, Austria;14. University Medical Center Schleswig‐Holstein, Department of General and Thoracic Surgery, Kiel, Germany;15. University Hospital Regensburg, Department of Surgery, Regensburg, Germany;16. Novartis Pharma GmbH, Nuremberg, Germany |
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| Abstract: | Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal‐sparing alternative. In this randomized 1‐year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post‐LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft‐Gault formula (?2.9 mL/min in favor of EVR, 95%‐CI: [?10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (?7.8 mL/min, 95%‐CI: [?14.366; ?1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy‐proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI‐based to EVR‐based immunosuppression proved to be a safe alternative post‐LTx that deserves further investigation in terms of nephroprotection. |
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| Keywords: | Calcineurin inhibitor agents conversion everolimus Liver transplantation mTor inhibitor renal function |
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