MO980OUTCOMES OF RABBIT ANTI-THYMOCYTE GLOBULIN VERSUS IL-2 RECEPTOR ANTAGONIST INDUCTION THERAPIES IN 2DR MISMATCH RENAL TRANSPLANT RECIPIENTS

Abstract

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method This was a retrospective cohort study using data from the United States Organ Procurement and Transplantation Network, all 2 DR mismatched RTRs who were maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2005 and 2015 were included. Follow up data was until September 2020. Patients who received transplants from living donors were included in the study. Collected data included recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (delayed graft function, cold ischemia time, number of previous transplants, panel reactive antibodies, HLA-mismatches, induction therapies, maintenance immunotherapy, and donor factors (donor type, donor age). RTRs were divided into 2 groups: based on induction therapy r-ATG and IL-2RA. Instrumental variable regression models were used to assess effect of induction therapy on acute rejection episodes at 6 months post-transplant and on graft survival. Type of induction therapy was instrumented for the transplant centre to reduce the centre effect on the choice of the induction therapy. Cox proportional hazard regression analysis was performed to assess the effect of induction therapy on graft survival. The regression models were adjusted for collected recipient, donor and transplant factors. Results 3052 patients received IL2-RA while 5143 patients received R-ATG induction. Using instrumental variables regression models, there were no significant differences between IL2-RA versus R-ATG induction in acute rejection episodes (OR=1.49, 95% CI ranges from 0.73 to 3.05, P=0.27), or graft survival (coefficient=0.95, 95% CI: -0.18 to 2.10, P=0.10). Using Cox proportional hazards regression, there was no significant difference in graft survival between either induction therapies (HR=0.90, 95% CI: 0.74 to 1.09, P=0.29). Conclusion This study showed no significant difference in acute rejection episodes or graft survival when using ATG or IL-2RA in 2DR HLA mismatched renal transplant recipients in the current tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to R–ATG induction therapy. Moreover, this study also highlights the fact that antigen level 2DR mismatches are not a risk factor for rejection and HLA matching should be based on epitope level rather than antigen level.