PROMISING EARLY OUTCOMES WITH A NOVEL, COMPLETE STEROID AVOIDANCE IMMUNOSUPPRESSION PROTOCOL IN PEDIATRIC RENAL TRANSPLANTATION1
PROMISING EARLY OUTCOMES WITH A NOVEL, COMPLETE STEROID AVOIDANCE IMMUNOSUPPRESSION PROTOCOL IN PEDIATRIC RENAL TRANSPLANTATION1
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新型、完全避免类固醇免疫抑制方案在儿科肾移植中带来良好的早期结果1
作者：
M. Sarwal;P. Yorgin;S. Alexander;M. Millan;A. Belson;Natasha Belanger;Laura Granucci;Cyd Major;Cathy Costaglio;Jaime Sánchez;P. Orlandi;O. Salvatierra
背景尽管皮质类固醇有不良副作用，但四十年来它一直是免疫抑制的基石。过去尝试在儿童肾移植中停用类固醇几乎没有成功。这项研究测试的假设是，一个完整的无类固醇的免疫抑制方案避免类固醇依赖抑制免疫反应，其伴随的急性排斥反应的风险类固醇撤出。方法.在10例首次肾移植的未致敏儿童受者（年龄5-21岁，平均14.4岁）中进行了一项完全避免类固醇免疫抑制方案的开放性前瞻性研究。类固醇被延长的达克珠单抗使用替代，与他克莫司和吗替麦考酚酯联合使用。无激素组在移植后0、1、3、6和12个月进行活检。将临床结果与37个匹配的历史对照的基于类固醇的组进行比较。结果两组移植物和患者存活率均为100%。无类固醇组在平均随访9个月（范围3-13.7个月）时没有临床急性排斥反应。无类固醇组的方案活检（包括3个月时的10名患者、6个月时的7名患者和12个月时的4名患者）仅显示2例轻度（Banff 1A）亚临床排斥反应（仅通过免疫抑制的名义增加即可逆转）并且没有慢性排斥反应。在6个月时，无类固醇组没有需要治疗的高血压（P =0.003），没有高胆固醇血症（P =0.007），基本上没有身体毁容（P =0.0001）。无类固醇组的血清肌酐、Schwartz GFR和平均Δ身高Z评分趋势更好。在无类固醇组中，1名患者在1个月时患有巨细胞病毒病，3名患者易于治疗单纯疱疹性口腔炎，但细菌感染或再住院率与类固醇组相比没有显著增加。无类固醇组在移植后早期贫血更多（P =0.004），表明类固醇在红细胞生成中的早期作用;促红细胞生成素使用正常的红细胞压积6个月。结论.完全无类固醇免疫抑制在这组儿童中是有效和安全的，没有早期临床急性排斥反应。该方案避免了类固醇的病态副作用，而不增加感染，并可能在避免不依从性方面发挥关键作用，尽管优化了肾功能和生长。
Background. Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. Methods. An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5–21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. Results. Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3–13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P =0.003), no hypercholesterolemia (P =0.007), and essentially no body disfigurement (P =0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P =0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. Conclusions. Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.