Kozody Macrae, Ortiz Jorge, Yu Yang, Bhalla Arnav, Katasani Hamsini, Herdrich Kyle, Li Meng-Hao, Koizumi Naoru, Faddoul Geovani
Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.
Department of Surgery, Garnet Health Medical Center, Middletown, New York.
J Surg Res. 2025 Jul;311:203-211. doi: 10.1016/j.jss.2025.04.026. Epub 2025 May 28.
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.
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.
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.
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.
使用抗胸腺细胞球蛋白（ATG）、阿仑单抗或白细胞介素-2受体抗体（IL2Ra）进行单药诱导是肾移植（KTX）期间免疫抑制的标准做法。ATG + IL2Ra的双重诱导治疗（DIT）偶尔作为特定中心方案的一部分或在ATG或IL2Ra诱导失败后的挽救措施使用。我们报告了单药方案与DIT的结果。
对2000年1月1日至2024年6月30日的器官共享联合网络（UNOS）数据库进行分析，重点关注接受ATG、阿仑单抗、IL2Ra或DIT诱导的KTX受者。记录受者和供者的特征。通过Kaplan-Meier生存曲线和回归分析比较不同诱导治疗的主要和次要终点。结果根据活体（LDKT）或 deceased（DDKT）供体状态进行分层。
在296,910例KTX受者中，3.6%接受了DIT诱导，58.1%接受了ATG诱导，14.1%接受了阿仑单抗诱导，24.3%接受了IL2Ra诱导。与其他方案相比，DIT受者的人类白细胞抗原错配最高，肾脏供体特征指数最高，冷缺血时间最长。与ATG相比，DIT与急性排斥反应增加（风险比（HR）：DDKT为1.449，LDKT为1.366）、移植肾功能延迟（比值比：DDKT为1.170，LDKT为3.765）和移植失败（HR：DDKT为1.184，LDKT为1.176）相关，且DDKT死亡率更差（HR为1.148）。DIT与巨细胞病毒感染和移植后淋巴细胞增生性疾病发生率降低、住院时间延长以及再次住院时间无变化相关。
与单药诱导相比，DIT与住院时间延长、移植肾功能延迟、急性排斥反应、移植失败和死亡率的风险更高相关。需要通过随机对照试验进行进一步研究以评估因果关系。
