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尸体供肾与活体供肾小儿肾移植中无抗体诱导的霉酚酸酯治疗

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation.

作者信息

Ojogho O, Sahney S, Cutler D, Baron P W, Abdelhalim F M, Hasan S M, Concepcion W

机构信息

Transplantation Institute, Loma Linda University Medical Center, Loma Linda, California 92354, USA.

出版信息

Pediatr Transplant. 2003 Apr;7(2):137-41. doi: 10.1034/j.1399-3046.2003.00035.x.

Abstract

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.

摘要

霉酚酸酯(MMF)是一种新型免疫抑制剂,它通过有效选择性抑制肌苷单磷酸脱氢酶来阻断T和B淋巴细胞中嘌呤的从头合成。已证明MMF可显著降低成人和儿童肾移植中急性排斥反应的发生率。MMF对儿童肾移植中常规抗体诱导治疗的影响尚未明确。值得注意的是,最近一项北美儿科移植合作研究得出结论,对于接受MMF的患者,T细胞抗体诱导治疗是有害的。我们的研究探讨了在不断发展的免疫抑制策略中使用MMF,以避免在活体(LD)和尸体(CAD)供体儿童肾移植中进行抗体诱导。我们回顾性分析了1996年11月至2000年4月期间43例接受基于MMF的三联疗法且未进行抗体诱导治疗的儿童肾移植记录。我们将CAD组(n = 17)与LD组(n = 26)进行了比较。两组在人口统计学上相似,只是CAD组的供体比LD组明显年轻,分别为26.1±13.7岁和36.2±9.2岁(p = 0.006)。所有患者均接受MMF,剂量为600 mg/m²/每日两次(最大剂量为2 g/d),并联合泼尼松与环孢素(86%)或他克莫司(14%)。每组的平均随访时间均超过36个月。6个月时的急性排斥反应发生率,CAD组为11.8%,LD组为15.4%(p = 0.999);1年时,CAD组为23.5%,LD组为26.9%(p = 0.999)。6个月时的平均估计肾小球滤过率(ml/min/1.73 m²),CAD组为73.3±15.3,LD组为87.6±24.2(p = 0.068)。CAD组1年、2年和3年的患者生存率分别为100%、100%和100%,LD组分别为100%、96%和96%。CAD组1年、2年和3年的移植物生存率分别为100%、100%和94%,LD组分别为96%、88%和71%。CAD组的移植物丢失是由于慢性排斥(n = 2),而LD组是由于不依从(n = 6)、移植后淋巴细胞增生性疾病(n = 1)和败血症(n = 1)。总之,在CAD和LD儿童肾移植中不进行抗体诱导的MMF在移植后6个月和1年时对急性排斥反应提供了统计学上相似且有效的预防。短期患者和移植物生存率极佳,然而,不依从仍然是长期移植物存活的严重挑战。需要更多对照研究来确定不进行抗体诱导治疗的MMF在儿童肾移植中的作用。

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