title: ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus.
abstract: ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2).
authors.affiliation: Republican Scientific and Practical Center (RSPC) for Organ and Tissue Transplantation, Minsk, Belarus.
authors.forename: Oleg O
authors.initials: OO
authors.lastname: Rummo
authors.affiliation: Department of Medical, Surgical and Neuroscience, Policlinico Santa Maria alle Scotte, University of Siena, Siena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Carmellini
authors.affiliation: Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, INSERM U563, IFR-BMT, CHU Purpan, Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: Department of Internal Medicine III, Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.affiliation: Department of Internal Medicine/Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Maarten H L
authors.initials: MH
authors.lastname: Christiaans
authors.affiliation: Department of Nephrology-Transplantation, University Hospital, Dijon, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mousson
authors.affiliation: Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Langer
authors.affiliation: Department of Surgery, Renal Transplantation, Catholic University, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Citterio
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, University Hospital of Bicêtre, Le Kremlin Bicetre, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.affiliation: Medical Affairs - Global, Astellas Pharma, Northbrook, IL, USA.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Brown
authors.affiliation: Astellas Pharma Europe Ltd, Chertsey, UK.
authors.forename: Gbenga
authors.initials: G
authors.lastname: Kazeem
authors.affiliation: General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D020123:Sirolimus / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus
keywords: calcineurin antagonists; immunosuppression; kidney clinical; outcome