单剂CD25单克隆抗体联合小剂量抗胸腺淋巴细胞球蛋白在肾移植中的应用

Efficiency of single-dose CD25 monoclonal antibody with low dose anti-human T-lymphocyte immunoglobulin in renal transplantation

目的 探讨单剂CD25单克隆抗体（舒莱/赛呢哌）联合小剂量兔抗胸腺淋巴细胞球蛋白（ATG）免疫诱导方案在肾移植中应用的临床效果。方法 回顾性分析我院2000年1月至2006年12月所完成的741例肾移植患者,分为2组。诱导组,448例,应用＂CD25单克隆抗体＋ATG＂免疫诱导方案,其中141例属高危人群。CD25单克隆抗体（舒莱/赛呢哌）为单剂,术前2h内静脉滴注;ATG共500mg,手术当天及术后？2d,100mg/d,静脉滴注,术后第3~6天,50mg/d,静脉滴注;术后免疫抑制剂减量;对照组,293例,未应用＂CD25单克隆抗体＋ATG＂免疫诱导。两组术后常规应用环孢素A（CsA）或他克莫司（FK506）＋吗替麦考酚酯？（MMF）＋泼尼松（Pred）＂三联＂免疫抑制方案。用卡方检验比较诱导组与对照组的临床效果和并发症的发生率差异的统计学意义。结果 诱导组,（1）普通人群（非高危人群）急性排斥反应（AR）发生率8.1﹪（25/307）,逆转率为100﹪（25/25）;感染发生率7.2﹪（22/307）,无巨细胞病毒（CMV）感染;术后1年人（肾）存活率99.7﹪/99.7﹪;（2）高危人群AR发生率14.9﹪（21/141）,逆转率为90.5﹪（19/21）;感染发生率13.5﹪（19/141）,其中确诊CMV感染1例;术后1年人（肾）存活率96.5﹪/95.0﹪。对照组,AR发生率14.7﹪（43/293）,逆转率88.4﹪（38/43）;感染发生率15.4﹪（45/293）,其中CMV感染2例;术后1年人（肾）存活率97.6﹪/95.9﹪。普通人群中,诱导组的AR发生率、感染发生率及人（肾）存活率与对照组比较差异有统计学意义（c2=7.424,P=0.024;c2=10.401,P=0.006;c2=7.468,P=0.024）。结论 单剂CD25单克隆抗体联合小剂量ATG方案在肾移植免疫诱导中具有重要的临床应用价值,可降低术后1年内AR发生率、降低感染发生率,提高1年人（肾）存活率,尤其适于高危人群。

Objective To evaluate the safety and efficiency of single-dose CD25 Mab （Simulete/Zenapax） combined with low-dose anti-human T-lymphocyte globulin （ATG） as induction therapy in kidney transplant recipients （especially the high-risk ones）. Methods A retrospective analysis of 741 cases of kidney transplant recipients in our hospital from January 2000 to December 2006 was performed. The recipients were divided into two groups. Patients in induction group （n = 448） received CD25 Mab ＋ ATG and there were 141 high-risk recipients. CD25 Mab was given intravenously within 2 hours pretransplant and ATG was given intravenously within 7 days （100 mg pretransplant, 1st and 2nd day posttransplant; 50 mg from 3rd to 6th day posttransplant）; Low dose of immunosuppressant was given after transplantation. Patients in control group （n = 293） received CsA/FK506 ＋ MMF ＋ Pred. All patients were followed up for at least 12 months. The clinical efficiency （one-year survival, acute rejection rate, infection rate, serum creatinine level and WBC） and safety profile were compared between the two groups. Results For low-risk patients in induction group, incidence of acute rejection was 8.1% （25/307） and all were cured. Infection rate was 7.2 % （22/307） and no CMV infection was observed. One year recipient/renal survival rate was 99.7 %/99.7 %. For high-risk patients in induction group one year recipient/renal survival rate was 96.5 %/95.0 %; Incidence of acute rejection was 14.9%（21/141） and 90.5 %（19/21） was cured. Infection rate was 13.5 %（19/141）, with one CMV infection. In control group, one year recipient/renal survival rate was 97.6 %/ 95.9 %. Incidence of acute rejection was 14.7 % （43/293） and 88.4 % （38/43） was cured. Infection rate was 15.4 % （45/293） and 2 cases of CMV infection were diagnosed. At days 3 and 7, WBC in the induction groups were （8.88 ± 3.34）× 109/L and （7.03± 3.24）× 109/L respectively, lower than those of control group （P = 0.002, 0.007）. At days 3 and 7, lymphocyte count in the induction groups were （0.47 ± 0.23）×109/L and （0.74 ± 0.41）× 109/L respectively, lower than those of control group（P = 0.000）. No difference was noted at day 10. There was significant difference in incidence of acute rejection, infection rate, survival rate and kidney survival rate between the control group and low-risk patients in induction group. Conclusion The induction therapy with single-dose CD25 Mab and low-dose ATG has important role in renal transplantation, particularly for high-risk recipients. This induction therapy can decrease the incidence of acute rejection and infection, leading to a higher person/kidney survival rate.