Background: Induction therapy with interleukin-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT in the modern immunosuppression era.

Design: We studied OPTN registry data for LRT from 2000 to 2012 maintained on tacrolimus/mycophenolic acid (TAC/MPA) at discharge to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction therapies: IL2-RA, rabbit anti-thymocyte globulin (rATG), and no antibody induction in steroid group versus IL2-RA, r-ATG and alemtuzumab in no-steroid group. The main outcomes were the risks of acute rejection at one-year and overall allograft failure (graft failure and death) at five-years post transplantation. We controlled for potential selection bias due to non-random assignment of induction therapies using the propensity score (PS) weighted analysis based on pre-treatment significant covariates.

Results: By multivariate logistic and Cox analysis adjusted for PS and covariates, in the steroid group, the outcomes were similar between IL2-RA and no antibody induction categories. When steroids were absent, the odds of acute rejection with rATG (OR = 0.73, 95% CI 0.59-0.90) and alemtuzumab (OR = 0.53, 95% CI 0.42-0.67) were lower, however, overall allograft failure risk was higher with alemtuzumab (HR = 1.27, 95% CI 1.03-1.56), but not with rATG (HR =1.19, 95% CI 0.97-1.45), compared with IL2-RA induction.

Conclusion: In LRT recipients, when TAC/MPA/Steroids are used, IL2-RA induction does not have any beneficial effect on outcomes. r-ATG can replace IL2-RA in steroid avoidance protocols.

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