*Department of Pharmacy Services, †Division of Transplant Surgery, ‡Division of Pathology and Laboratory Medicine, and §Division of Nephrology, Medical University of South Carolina, Charleston, SC.
Ann Surg. 2014 May;259(5):888-93. doi: 10.1097/SLA.0000000000000496.
The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression.
The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear.
This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor.
A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients.
RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).
本研究旨在确定兔抗胸腺细胞球蛋白（RATG）与白细胞介素-2 受体拮抗剂在接受现代免疫抑制治疗的多种族肾移植患者中的安全性和疗效。
在现代免疫抑制条件下，应用流式细胞术进行交叉配型，对于排斥反应风险高的患者（尤其是黑人受者），最佳的诱导治疗方案仍不明确。
这是一项前瞻性、风险分层、随机、单中心、开放性研究，共纳入 200 例连续就诊于大型学术教学中心的患者。患者随机接受达昔单抗或巴利昔单抗或 RATG 诱导治疗，联合他克莫司、霉酚酸酯和皮质类固醇。在各组之间进行分层，以确保每组的黑人、再次移植、高群体反应性抗体（PRA）（>20%）和冷缺血时间延长（>24 小时）患者数量相等。主要观察指标为治疗效果，定义为活检证实的急性排斥反应发生率和估计的肌酐清除率。患者接受 12 个月的随访。如果成年（≥18 岁）患者接受来自已故、活体非亲属或非人类白细胞抗原相同的活体亲属供者的同种异体移植物，则将其纳入肾移植受者。
共纳入 200 例患者（白细胞介素-2 受体拮抗剂组 n = 98 例，RATG 组 n = 102 例），患者入组时间为 2009 年 2 月至 2011 年 7 月。两组患者的 1 年急性排斥反应发生率较低且相似（白细胞介素-2 受体拮抗剂组为 10%，RATG 组为 6%；P = 0.30）。两组的肌酐清除率也相似（白细胞介素-2 受体拮抗剂组 56 ± 20 mL/min/1.73 m2，RATG 组 55 ± 22 mL/min/1.73 m2；P = 0.73）。受者种族的亚组分析显示，仅 RATG 可预防黑人患者 6 个月和 12 个月的急性排斥反应，且不会增加感染风险。诱导治疗并不影响根据受者计算的 PRA 确定的排斥反应率；然而，RATG 与低 PRA 患者的 BK 病毒感染风险增加有关。
RATG 诱导治疗可显著降低黑人肾移植受者的早期急性排斥反应发生率，而致敏患者似乎并未从该治疗中获益。本研究已在 Clinicaltrials.gov 注册（NCT00859131）。
