Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.
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.
Calmus
Yvon
Y
Unité de Transplantation Hépatique, Hôpital Saint-Antoine, Paris, France. yvon.calmus@sat.aphp.fr
Kamar
Nassim
N
Gugenheim
Jean
J
Duvoux
Christophe
C
Ducerf
Christian
C
Wolf
Philippe
P
Samuel
Didier
D
Vanlemmens
Claire
C
Neau-Cransac
Martine
M
Salamé
Ephrem
E
Chazouillères
Olivier
O
Declerck
Nicole
N
Pageaux
Georges-Philippe
GP
Dubel
Laurence
L
Rostaing
Lionel
L
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003404:Creatinine / Q000097:blood; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008099:Liver / Q000187:drug effects* / Q000502:physiology*; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013256:Steroids; D003404:Creatinine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus