他克莫司在胰、肾同期联合移植中的应用体会

The use of tacrolimus in simultaneous pancreas-kidney transplantation:a single-centre experience in China

目的回顾性总结他克莫司(FK506)在胰、肾同期联合移植(SPK)中的应用经验。方法37例SPK受者,术后早期采用抗淋巴细胞球蛋白(最初3例)或抗白细胞介素2受体单克隆抗体(34例)诱导治疗,采用FK506、霉酚酸酯(MMF)和皮质激素维持治疗。FK506于术后第3～4天开始口服,起始剂量为0.05～0.08 mg·kg^(-1)·d^(-1),3～5 d后根据血药浓度调整用量,血FK506的浓度谷值,术后1个月内维持在10～12μg/L,2～3个月为6～10μg/L,3个月后为4～8μg/L。结果37例术后均停用胰岛素,仅1例(2.7%,1/37)术后6个月死于急性心肌梗死,受者、移植胰和移植肾1年存活率均为97%。空腹血糖恢复正常的时间为(13.4±8.9)d。28例1型糖尿病患者术后空腹血糖恢复正常的时间为(9.7±3.2)d,9例2型糖尿病患者术后空腹血糖恢复正常的时间显著延长,为(23.0±11.7)d。1年内急性排斥反应发生率为13.5%(5/37),其中4例为单纯移植肾排斥反应,1例同时累及移植胰腺和肾脏;2例经激素冲击治疗后逆转,1例经激素和抗淋巴细胞球蛋白治疗逆转,另2例经激素冲击治疗后,血肌酐一度下降,但2～3个月后因再次发生排斥反应,血肌酐逐渐上升,恢复血液透析,但移植胰功能良好,其后行再次肾移植。结论以FK506为基础的免疫抑制能安全、有效地预防SPK后的排斥反应。

Objective To summarize the experience with use of tacrolimus （FK506） in diabetic patients with end-stage renal disease undergoing their first cadaveric simultaneous pancreas-kidney （SPK） transplantation. Methods Thirty-seven patients undergoing SPK received antilymphocyte globulin （first 3 cases） or anti-IL-2R monoclonal antibody （last 34 cases） for induction. Immunosuppression was maintained with FK506, mycophenolate mofetil （MMF）, and corticosteroids. FK506 was administered on the postoperative day 3-4 in an initial oral dose of 0. 05-0. 08 mg· kg^-1 ·d^-1 and continued at the necessary dose to maintain blood trough levels within accepted therapeutic limits. FKS06 12 h trough levels were targeted to be 10-12μg/L （by monoclonal TDX） during the first month, 6-10 μg/L between the second and third month and then 4-8 μg/L for the rest of years. Results All 37 patients experienced good function of pancreas grafts and no further insulin treatment. Only one recipient （2.7 %） died due to myocardiac infarction at 6th month posttransplant. Patient, pancreas graft and kidney graft one-year survival rate was 97 %. Five patients （13. 5 % ） had biopsy-proven renal rejection episodes. One rejection episode was treated with steroids and ATG. Other rejection episodes were treated with steroids alone. Two patients lost their kidney grafts 2-3 months after the second rejection episodes and received retransplants. Conclusion FK506-based immunosuppressive regiment after SPK is effective and safe to prevent rejection, and can be used as a preferred, maintenance immunosuppressive in SPK.