Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.
Author(s): Calmus Y, Kamar N, Gugenheim J, Duvoux C, Ducerf C, Wolf P, Samuel D, Vanlemmens C, Neau-Cransac M, Salame E, Chazouilleres O, Declerck N, Pageaux GP, Dubel L, Rostaing L
Affiliation(s): Unite de Transplantation Hepatique, Hopital Saint-Antoine, Paris, France. email@example.com
Publication date & source: 2010-06-27, Transplantation., 89(12):1504-10.
Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
BACKGROUND: Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. METHODS: This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. RESULTS: The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (<or=100micromol/L or >100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. CONCLUSIONS: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.