Tanriover Bekir, Zhang Song, MacConmara Malcolm, Gao Ang, Sandikci Burhaneddin, Ayvaci Mehmet U S, Mete Mutlu, Tsapepas Demetra, Rajora Nilum, Mohan Prince, Lakhia Ronak, Lu Christopher Y, Vazquez Miguel
Division of Nephrology,
Department of Clinical Sciences, and.
Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1041-9. doi: 10.2215/CJN.08710814. Epub 2015 May 15.
Induction therapy with IL-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 with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) 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 approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies.
Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction.
Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.
白细胞介素-2受体拮抗剂（IL2-RA）诱导治疗被推荐为活体供肾移植（LRT）的一线用药。然而，在使用他克莫司（TAC）/霉酚酸（MPA）联合或不联合类固醇的LRT中，IL2-RA的使用仍存在争议。
设计、地点、参与者及测量指标：对器官获取与移植网络登记处2000年至2012年接受LRT且出院时维持使用TAC/MPA的患者（n = 36,153）进行研究，以比较IL2-RA与其他诱导方案的有效性。该队列最初根据出院时维持使用类固醇的情况分为两组：使用类固醇组（n = 25,996）和不使用类固醇组（n = 10,157）。每组再根据常用的抗体诱导方法进一步分为三类：使用类固醇组中的IL2-RA、兔抗胸腺细胞球蛋白（r-ATG）和无诱导，不使用类固醇组中的IL2-RA、r-ATG和阿仑单抗。主要结局为移植后1年急性排斥反应风险以及随访结束时总体移植失败（移植失败或死亡）情况。倾向评分加权回归分析用于尽量减少因诱导治疗非随机分配导致的选择偏倚。
对倾向评分进行调整的多变量逻辑回归和Cox分析显示，使用类固醇组中无诱导组（急性排斥反应的比值比[OR]为0.96；95%置信区间[95%CI]为0.86至1.08；总体移植失败的风险比[HR]为0.99；95%CI为0.90至1.08）和IL2-RA组的结局相似。在不使用类固醇组中，r-ATG（OR为0.73；95%CI为0.59至0.90）和阿仑单抗（OR为0.53；95%CI为0.42至0.67）的急性排斥反应几率较低；然而，与IL2-RA诱导相比，阿仑单抗总体移植失败风险较高（HR为1.27；95%CI为1.03至1.56），而r-ATG则不然（HR为1.19；95%CI为0.97至1.45）。
与无诱导治疗相比，在LRT受者中使用TAC/MPA/类固醇时，IL2-RA诱导与更好的结局无关。在避免使用类固醇的方案中，r-ATG似乎是IL2-RA可接受的且可能是首选的诱导替代方案。
