Combined Thymoglobulin and Interleukin-2 Receptor Antagonist Induction Therapy in Kidney Transplantation Is Associated With Worse Delayed Graft Function, Acute Rejection, Graft Loss, and Mortality.

INTRODUCTION

Single-agent induction with either Thymoglobulin (ATG), alemtuzumab, or interleukin-2 receptor antibodies (IL2Ra) is a standard of immunosuppression during kidney transplantation (KTX). Dual-induction therapy (DIT) with ATG + IL2Ra is occasionally administered as part of a center-specific protocol or salvage following failed ATG or IL2Ra induction. We report the outcomes of single-agent regimens versus DIT.

METHODS

Analysis of the UNOS database from January 1, 2000, to June 30, 2024, focused on KTX recipients induced with ATG, alemtuzumab, IL2Ra, or DIT. Recipient and donor characteristics were recorded. Primary and secondary endpoints were compared across induction therapies with Kaplan-Meier survival curves and regression analysis. Outcomes were stratified based on living (LDKT) or deceased (DDKT) donor status.

RESULTS

Of the 296,910 KTX recipients, 3.6% were induced with DIT, 58.1% ATG, 14.1% alemtuzumab and 24.3% with IL2Ra. Compared to other regimens, DIT recipients had the highest human leukocyte antigen mismatch, highest Kidney Donor Profile Index and longest cold ischemia time. DIT was associated with increased acute rejection (hazard ratio (HR) 1.449 DDKT, HR 1.366 LDKT), delayed graft function (odds ratio 1.170 DDKT, odds ratio 3.765 LDKT) and graft failure (HR 1.184 DDKT, HR 1.176 LDKT) and worse DDKT mortality (HR 1.148) compared to ATG. DIT correlated with reduced cytomegalovirus and post-transplant lymphoproliferative disorder occurrence, increased length of stay and no change in time to rehospitalization.

CONCLUSIONS

DIT was associated with higher risk of prolonged hospitalization, delayed graft function, acute rejection, graft failure and mortality compared to single drug induction. Further investigation with a randomized controlled trial is required to assess causation.