肾移植术后单剂应用人源化抗CD3单克隆抗体的临床观察

Clinical study of single-dose of recombinant humanized anti-CD3 monoclonal antibody injection in kidney transplant recipients

目的研究肾移植受者体内应用人源化抗CD3单克隆抗体（OKT3）注射液单次剂量递增给药后的短期和长期安全性。方法2008年6—12月，共29例肾功能稳定的尸体肾移植受者入选该研究。每位受试者按人组顺序随机分至2．5mg（n=9）、5．0mg（n=10）、10．0mg（n=10）3个剂量组，并于移植术后7～14d内接受相应剂量的OKT3单次给药。同时选取同期未参加试验的30例。肾移植受者作为对照组。所有患者至少随访2年，随访期间监测肝功能、。肾功能、血常规等指标，并观察有无其他不良事件。结果各剂量组受试者在给药后48h内，出现低热（7／29）、畏寒（4／29）、肝功能损害（2／29）、上呼吸道感染（1／29）和头痛（1／29），未出现明显的首剂效应，其余的不良反应轻微，发生率与剂量无关。随访期间内，试验组和对照组2-年人／肾长期存活率分别为100％／100％和100％／97％；移植肾活检证实的急性排斥发生率分别为6．9％（2／29）和10．0％（3／30），肺部感染发生率分别为10．3％（3／29）和13．3％（4／30）。术后1周及3、6、12、24个月监测血肌酐值显示，两组差异均无统计学意义（均P〉0．05）。结论人源化OKT3不同剂量单次给药在肾移植受者体内安全性良好，其有望成为一种抗排斥能力强、毒副作用较小的免疫抑制剂。

Objective To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody （OKT3） in kidney transplantation recipients. Methods A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2. 5 mg （ n = 9 ）, 5.0 mg （ n = 10） and 10. 0 mg （ n = 10） at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period. All patients were followed up for at least 2 years. During this period, liver function, kidney function, hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. Results No obvious first dose effect was observed, except low heat （7/29）, chills （4/29） , mild liver damage （2/ 29） , upper respiratory tract infection and headache （1/29） across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/ grafts survival rates of treatment goup and control group were 100% / 100%, and 100% / 97% , respectively. The incidence of acute rejection confirmed by renal biopsy was 6. 9% （2/29） and 10. 0% （3/30） in treatment group and control group, respectively. The incidence of lung infection was 10. 3% （3/29） and 13.3% （4/30）, respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups （ all P 〉 0. 05 ）. Conclusion It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.