title: Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.
abstract: DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids).
  
  
  METHODS
  eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable.
authors.affiliation: Transplantcentre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: TruneČka
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Klempnauer
authors.affiliation: Department of Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany.
authors.forename: W O
authors.initials: WO
authors.lastname: Bechstein
authors.affiliation: Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Pirenne
authors.affiliation: The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Friman
authors.affiliation: Department of Abdominal Surgery, A.V. Vishnevsky Institute of Surgery, Moscow, Russian Federation.
authors.forename: A
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Isoniemi
authors.affiliation: Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: Department of General, Visceral and Vascular Surgery, Jena University Hospital, Thuringia, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Department of Surgery, Goethe University Hospital and Clinics, Frankfurt, Germany.|Department of General, Visceral and Transplantation Surgery, Westpfalz-Klinikum Hospital, Kaiserslautern, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mönch
authors.affiliation: Astellas Pharma Inc., Northbrook, IL.
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.affiliation: Astellas Pharma Europe Ltd, London, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Undre
authors.affiliation: Liver Transplant Unit, Policlinico di Tor Vergata, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tisone
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008099:Liver / Q000502:physiology*; D008107:Liver Diseases / Q000503:physiopathology / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: calcineurin inhibitor; clinical research/practice; clinical trial; glomerular filtration rate (GFR); immunosuppressant; immunosuppression/immune modulation; liver allograft function/dysfunction; liver transplantation/hepatology; liver transplantation: split; tacrolimus