免疫吸附和他克莫司、霉酚酸酯及甲泼尼龙联合治疗移植肾加速性排斥反应

Immunoadsorption and tacrolimus-mycophenolate-methylprednisolone rescue for accelerated acute rejection in kindeny transplantation

目的 :探讨移植肾加速性排斥反应 (acceleratedacuterejection ,AccAR)的治疗方法。 方法 :在该院 2 0 0 1年12月至 2 0 0 3年 6月间 196例肾移植患者中 ,有 2例术前群体反应性抗体 (PRA)曾经为高敏状态 ,术后结合临床和病理证实为AccAR。其诊断依据为 :①发生在肾移植术后 3～ 5天内 ;②血肌酐 (SCr)迅速升高 ;③典型病理改变为肾小管周围毛细血管 (peritubularcapillary ,PTC)内补体裂解片段C4d沉积和PTC内中性粒细胞积聚 ,毛细血管纤维蛋白沉积或血栓形成 ,动脉内膜炎或 (和 )血管炎 ,血管壁免疫球蛋白和其他补体片段沉积。 2例患者均立即采用免疫吸附 (IA)和他克莫司 (Tacrolimus ,Tac,0 .15mg /kg·d 1,谷浓度 6～ 12 μg/L ) +霉酚酸酯 (MMF ,1.5～ 2g/d)+甲泼尼龙 (MP ,5 0 0mg/d× 3,静脉注射 )联合抗排斥治疗。 结果 :2例患者每次IA后各种免疫球蛋白 (以IgG为主 )及PRA 组织相容性抗原 Ⅰ (PRA HLA Ⅰ )、PRA HLA Ⅱ均明显下降。重复肾活检见排斥反应明显减轻 ,SCr分别在术后 1个月及半个月开始下降 ,术后 2个月和 1个月恢复正常 ,至今已分别随访 2 3个月及 14个月 ,病情稳定 ,SCr正常。 结论 :及时充分的IA与足够剂量的Tac、MMF及MP联合应用 ,是治疗移植肾AccAR的有效方法。

Objective:To explore an effective treatment for accelerated acute rejection in renal transplantation. Methods:Two of 196 renal allograft recipients transplanted at the authors' institute between December 2001 and Jun 2003 were identified with accelerated acute rejection (AccAR).The diagnosis was based on: ①Rejection episode between the first 3 to 5 postoperative days(PODs). ②Evidence of severe graft dysfunction. ③Typical pathologic features:a. C4d deposits in peritubular capillaries( PTC); b. accumulation of polymorphonuclear neutrophils in PTC; c. capillary fibrin; and d. endarteritis(intimal arteritis) and/or vasculitis.Both patients were treated with protein A immunoadsorption(IA) (Immunosorba, Fresenius, Germany)and tacrolimus-mycophenolate- methylprednisolone rescue immediately after diagnosis. 2-3 plasma volumes were processed during each IA session and recipients received every other day treatment sessions in the first 3-5 days and then one to two sessions per week. Immunosuppressant rescue therapy consisted of tacrolimus(Tac) (initial dose: 0.15 mg/kg·d -1 , trough whole-blood levels range 6-12 μg/L), mycophenolate mofetil (MMF)(1.5-2 g/day) and methylprednisolone (500 mg/d,iv, 3 d). Results:Durring treatment , a remarkable fall in IgG titers achieved in the first day with a decrease in IgM and IgA , a slight decrease in albumin ,and a negative PRA-HLA-I and PRA-HLA-II post-IA were found in both recipients after several IAs. Follow-up biopsies showed pathologic features disappeared or became less prominent. The graft function of these two patients dramatically improved and the creatinine levels returned to normal on PODs 60 and 30 respectively.Now the grafts functioned well ,and the creatinine levels were about 80 and 90 μmol/L followed-up 23 and 14 months post-transplant respectively. Conclusion:Our findings suggest that timely and sufficient IA combined with tacrolimus- mycophenolate-methylprednisolone rescue is an effective treatment for accelerated acute rejection.