title: Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study.
abstract: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data.
  
  
  
  PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment.
  
  
  
  A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively.
  
  
  
  Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.
authors.affiliation: Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sterneck
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Essen University Hospital, Essen, Germany.|Department of General and Visceral Surgery, St. Bernhard-Hospital Kamp-Lintfort, Kamp-Lintfort, Germany.
authors.forename: Gernot M
authors.initials: GM
authors.lastname: Kaiser
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Heyne
authors.affiliation: Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Richter
authors.affiliation: Department of General, Abdominal and Vascular Surgery, Jena University Hospital, Jena, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Rauchfuss
authors.affiliation: Clinic for General, Abdominal and Transplant Surgery, Charité University Medical Center Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.affiliation: Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Essen University Hospital, Essen, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Klein
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.affiliation: Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.affiliation: Department of General, Abdominal and Vascular Surgery, Jena University Hospital, Jena, Germany.
authors.forename: Utz
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gotthardt
authors.affiliation: Department of Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Loss
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ladenburger
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wimmer
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dworak
authors.affiliation: Department of Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007677:Kidney Function Tests; D008107:Liver Diseases / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus
keywords: calcineurin inhibitors; everolimus; long-term follow-up; renal function