The impact of IL2ra induction therapy in kidney transplantation using tacrolimus- and mycophenolate-based immunosuppression.
BACKGROUND
IL2 receptor antagonist (IL2ra) induction therapy has gained favor due to an excellent safety profile and improved outcomes in randomized trials using cyclosporine-based immunosuppression. However, there have been no large randomized trials or retrospective analyses examining the effect of IL2ra versus no induction using tacrolimus and mycophenolate (TAC/MPA)-based therapy.


METHODS
A retrospective analysis from the Scientific Renal Transplant Registry of adult, primary kidney transplant recipients from 2000 to 2008 with initial immunosuppression of TAC/MPA and prednisone, who received IL2ra induction therapy or no induction therapy (n=28,686) was performed. The primary outcome was acute rejection at 1 year, and secondary outcomes were graft and patient survival at 1 and 3 years. Multivariable analysis was used to control for factors shown to influence the incidence of acute rejection, and separate analyses were performed for deceased versus living donors.


RESULTS
Acute rejection at 1 year was significantly lower with IL2ra (11.6%) versus no induction therapy (13.0%; P=0.001). One-year (95.7% vs. 95.8%) and 3-year (87.5% vs. 87.8%) graft survival, and 1-year (97.4% vs. 97.5%) and 3-year (92.8% vs. 93.2%) patient survival, was not different between those receiving IL2ra and no induction therapy. On multivariable analysis, the relative risk of acute rejection with IL2ra was 0.90 (95% CI, 0.85-0.96; P=0.001), and the effect was greater in living donors (relative risk, 0.82; P<0.001) than deceased donors (relative risk, 0.95; P=0.23).


CONCLUSIONS
The benefit of IL2ra induction with TAC/MPA/prednisone maintenance immunosuppression is less than previously reported due to a low baseline incidence of acute rejection.
Gralla
Jane
J
Transplant Center, University of Colorado Denver, Aurora, CO 80045, USA.
Wiseman
Alexander C
AC
D000328:Adult; D002102:Cadaver; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors
C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus