阿仑单抗诱导治疗高度致敏的肾移植受者。

Alemtuzumab induction therapy in highly sensitized kidney transplant recipients.

机构信息

Department of Urology, Fuzhou General Hospital of Nanjing Command Chinese People's Liberation Army, Fuzhou, Fujian 350025, China.

出版信息

Chin Med J (Engl). 2011 Mar;124(5):664-8.

PMID:21518554

Abstract

BACKGROUND

Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.

METHODS

In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.

RESULTS

Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05).

CONCLUSION

Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.

摘要

背景

免疫高危肾移植患者的免疫抑制通常涉及抗胸腺细胞球蛋白诱导和三联药物维持治疗。阿仑单抗，一种人源化抗 CD52 抗体，有望成为肾移植的一种有前途的诱导治疗药物。然而，目前对于其疗效和安全性尚无共识。本研究旨在评估阿仑单抗作为高度致敏肾移植受者免疫诱导治疗的疗效和安全性。

方法

这是一项前瞻性、开放标签、随机、对照试验，共纳入 23 例高免疫风险患者（群体反应性抗体>20%）。他们分为两组：阿仑单抗组（试验组）和抗胸腺细胞球蛋白（ATG）组（对照组）。阿仑单抗组患者在再灌注前接受静脉注射阿仑单抗（15mg）单次剂量。术后 24 小时，给予另一种剂量的阿仑单抗（15mg）。对照组患者在肾移植前 2 小时给予兔抗胸腺细胞球蛋白（9mg/kg），持续至吻合完成时血管夹取出。两组的维持免疫抑制均采用包括他克莫司、泼尼松和霉酚酸酯（MMF）在内的标准三联疗法。在 2 年的随访期间，记录急性排斥反应（AR）和感染发作，并监测肾功能。采用 SPSS17.0 软件进行 χ(2)检验、t 检验和 Kaplan-Meier 分析。

结果

中位随访时间为 338 天。在阿仑单抗组和 ATG 组中，存活受者的肌酐和血尿素氮值相似（P>0.05）。阿仑单抗组白细胞计数在最多 6 个月的时间点显著降低（P<0.05）。一名接受阿仑单抗治疗的患者在术后第 65 天因急性心肌梗死死亡。两名 ATG 患者因严重肺部感染或心肺衰竭死亡。阿仑单抗组 2 年累积移植物存活率为 90.9%，ATG 组为 81.8%（P>0.05）。阿仑单抗组有 1 例移植物失功，ATG 组有 2 例移植物失功，所有移植物失功均归因于排斥反应。阿仑单抗组 2 年累积无排斥反应率为 81.8%，而 ATG 组为 72.7%（P>0.05）。