Cantarovich Diego
Department of Nephrology and Clinical Immunology, ITERT, Nantes University Hospital, Nantes, France.
J Nephrol. 2004 Nov-Dec;17 Suppl 8:S40-6.
We started using polyclonal antibody preparations (Thymoglobuline and Lymphoglobuline) as well as cyclosporine in 1981. A sequential immunosuppressive protocol was designed consisting of induction, delay cyclosporine introduction and corticosteroid withdrawal within the first 3 post-transplant months. This new immunosuppressive regimen has been applied to 1,671 patients: 1,439 received Thymoglobuline and 232 Lymphoglobuline; 1,083 were recipients of a primary renal transplant, 282 of a second transplant, 52 of third or fourth transplants, and 254 were recipients of a simultaneous kidney-pancreas transplant. The great majority of patients (96%) were recipients of cadaver organs; their age ranged from 3 to 77 years (average, 43+/-14). The overall incidence of acute rejection (intent-to-treat and biopsy-proven) was 23.7% (16% of patients had one episode and 8% had more than one episode), with 6.5% of rejections occurring after the third month and 3% after 12 months. The incidence of corticosteroid-resistant rejection was 8.7%. Between 1981 and 1990 (azathioprine maintenance) 40% of patients experienced an acute rejection while receiving a primary transplant versus 44% in case of retransplantation. Between 1991 and 1995 (CsA microemulsion maintenance), these percentages were reduced to 30 and 16%. After 1996 (mycophenolate mofetil and calcineurin inhibitors maintenance), the incidence of acute rejection was dramatically reduced to 8 and 6%, respectively in primary and retransplants. The incidence of patients free of corticosteroids was 61% at 3 months, 74% at 6 months, 79% at 1 year, 82% at 2 years, 89% at 5 years, 94% at 10 years and 100% at 20 years. A statistically better graft survival (up to 20 years, with similar patient survival) was observed in patients treated with Thymoglobuline as compared to Lymphoglobuline. Similar graft survival was observed in recipients of primary transplants as compared to retransplantation. The overall incidence of PTLD was 2.3%, with a significant decrease over the years achieving 0% after 1999. Thymoglobuline induction is a safe and highly efficient therapy to prevent rejection after kidney and kidney-pancreas transplantation. In association with CNI and antiproliferative immunosuppressive drugs, Thymoglobuline allowed the safe and early withdrawal of corticosteroids. This strategy of minimization of immunosuppression may have several beneficial effects in the long term.
1981年起，我们开始使用多克隆抗体制剂（即胸腺球蛋白和淋巴细胞球蛋白）以及环孢素。设计了一种序贯免疫抑制方案，包括诱导期、延迟引入环孢素以及在移植后的前3个月内停用皮质类固醇。这种新的免疫抑制方案已应用于1671例患者：1439例接受胸腺球蛋白治疗，232例接受淋巴细胞球蛋白治疗；1083例接受初次肾移植，282例接受二次移植，52例接受三次或四次移植，254例接受同期肾胰腺移植。绝大多数患者（96%）接受的是尸体器官；他们的年龄在3至77岁之间（平均43±14岁）。急性排斥反应（意向性治疗且经活检证实）的总体发生率为23.7%（16%的患者发生一次排斥反应，8%的患者发生不止一次排斥反应），其中6.5%的排斥反应发生在第三个月后，3%的排斥反应发生在12个月后。皮质类固醇抵抗性排斥反应的发生率为8.7%。1981年至1990年（硫唑嘌呤维持治疗），40%的初次移植患者在接受移植时发生急性排斥反应，二次移植患者的这一比例为44%。1991年至1995年（环孢素微乳剂维持治疗），这些比例分别降至30%和16%。1996年后（霉酚酸酯和钙调神经磷酸酶抑制剂维持治疗），初次移植和二次移植的急性排斥反应发生率分别大幅降至8%和6%。停用皮质类固醇的患者比例在3个月时为61%，6个月时为74%，1年时为79%，2年时为82%，5年时为89%，10年时为94%，20年时为100%。与淋巴细胞球蛋白治疗的患者相比，接受胸腺球蛋白治疗的患者观察到统计学上更好的移植物存活率（长达20年，患者存活率相似）。初次移植受者与二次移植受者的移植物存活率相似。移植后淋巴细胞增生性疾病（PTLD）的总体发生率为2.3%，多年来显著下降，1999年后降至0%。胸腺球蛋白诱导是预防肾移植和肾胰腺移植后排斥反应的一种安全且高效的治疗方法。与钙调神经磷酸酶抑制剂和抗增殖免疫抑制药物联合使用时，胸腺球蛋白可实现安全且早期停用皮质类固醇。这种免疫抑制最小化策略可能在长期内产生多种有益效果。
