Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the 'ReSpECT' study.
We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standard-dose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels </=8 ng/mL], and corticosteroids; n = 170); group C (daclizumab induction, MMF, reduced-dose tacrolimus delayed until the fifth day posttransplant and corticosteroids, n = 172). The primary endpoint was change from baseline in estimated glomerular filtration rate (eGFR) at 52 weeks. The eGFR decreased by 23.61, 21.22 and 13.63 mL/min in groups A, B and C, respectively (A vs C, p = 0.012; A vs B, p = 0.199). Renal dialysis was required less frequently in group C versus group A (4.2% vs. 9.9%; p = 0.037). Biopsy-proven acute rejection rates were 27.6%, 29.2% and 19.0%, respectively. Patient and graft survival was similar. In conclusion, daclizumab induction, MMF, corticosteroids and delayed reduced-dose tacrolimus was associated with less nephrotoxicity than therapy with standard-dose tacrolimus and corticosteroids without compromising efficacy or tolerability.
Neuberger
J M
JM
Liver Unit, Queen Elizabeth Hospital, Birmingham, UK. j.m.neuberger@bham.ac.uk
Mamelok
R D
RD
Neuhaus
P
P
Pirenne
J
J
Samuel
D
D
Isoniemi
H
H
Rostaing
L
L
Rimola
A
A
Marshall
S
S
Mayer
A D
AD
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011355:Prodrugs; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011355:Prodrugs; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus