title: Evaluation of renal function in liver transplant recipients receiving daclizumab (Zenapax), mycophenolate mofetil, and a delayed, low-dose tacrolimus regimen vs. a standard-dose tacrolimus and mycophenolate mofetil regimen: a multicenter randomized clinical trial.
abstract: Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low-dose tacrolimus (target trough level 4-8 ng/mL, starting day 4-6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end-points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m(2); P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m(2); P = 0.038). In conclusion, delayed low-dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post-liver transplantation without the cost of increased acute rejection.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada. eyoshida@interchange.ubc.ca
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Marotta
authors.forename: Paul D
authors.initials: PD
authors.lastname: Greig
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kneteman
authors.forename: Denis
authors.initials: D
authors.lastname: Marleau
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Kevork M
authors.initials: KM
authors.lastname: Peltekian
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Lilly
authors.forename: Charles H
authors.initials: CH
authors.lastname: Scudamore
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Bain
authors.forename: William J
authors.initials: WJ
authors.lastname: Wall
authors.forename: Andre
authors.initials: A
authors.lastname: Roy
authors.forename: Robert F
authors.initials: RF
authors.lastname: Balshaw
authors.forename: Jeffrey S T
authors.initials: JS
authors.lastname: Barkun
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D005260:Female; D048550:Hepatic Insufficiency / Q000601:surgery*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus