title: A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation--PROTECT.
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.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Hepatobiliary and Transplant Surgery, Hamburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: J
authors.initials: J
authors.lastname: Klempnauer
authors.forename: S
authors.initials: S
authors.lastname: Beckebaum
authors.forename: H J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: P
authors.initials: P
authors.lastname: Schemmer
authors.forename: U
authors.initials: U
authors.lastname: Settmacher
authors.forename: N
authors.initials: N
authors.lastname: Heyne
authors.forename: P-A
authors.initials: PA
authors.lastname: Clavien
authors.forename: F
authors.initials: F
authors.lastname: Muehlbacher
authors.forename: I
authors.initials: I
authors.lastname: Morard
authors.forename: H
authors.initials: H
authors.lastname: Wolters
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: T
authors.initials: T
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Sterneck
authors.forename: F
authors.initials: F
authors.lastname: Lehner
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: G
authors.initials: G
authors.lastname: Kazemier
authors.forename: A
authors.initials: A
authors.lastname: Pascher
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: F
authors.initials: F
authors.lastname: Rauchfuss
authors.forename: A
authors.initials: A
authors.lastname: Schnitzbauer
authors.forename: S
authors.initials: S
authors.lastname: Nadalin
authors.forename: M
authors.initials: M
authors.lastname: Hack
authors.forename: S
authors.initials: S
authors.lastname: Ladenburger
authors.forename: H J
authors.initials: HJ
authors.lastname: Schlitt
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus