Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation
Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation
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DOI：
10.1007/s00467-017-3725-1
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发表时间：
2017-11-01
影响因子：
3
通讯作者：
Pape, Lars
中科院分区：
文献类型：
--
作者：
Cihan, Yasemen;Kanzelmeyer, Nele;Pape, Lars
慢性抗体介导的排斥反应（cAMR）是晚期移植肾失功的主要原因，但目前的治疗方法往往无效。兔抗人胸腺细胞免疫球蛋白（rATG）可能是有用的，但它的使用几乎没有文献记载。方法回顾性分析9例儿童肾移植患者的资料，这些患者接受了rATG治疗（1.5 mg/kg x 5天），在对脉冲泼尼松龙、静脉注射免疫球蛋白、利妥昔单抗和增加免疫抑制强度无应答后，结果从确诊到cAMR的中位时间为179天。诊断后5-741天开始使用rATG。估计肾小球滤过率（eGFR）中位数从rATG开始时的40 mL/min/1.73 m2增加至9个月后的62 mL/min/1.73 m2（p = 0.039）。4例患者在9个月后显示eGFR显著升高，2例患者显示小幅改善; 3例患者在开始rATG后eGFR继续下降。随访期间无移植物丢失。在末次随访时，8例患者中有4例数据可用，不再检测到供体特异性抗体（DSA），8例患者中有1例患者的中位荧光强度大幅下降; 8例患者中有2例患者的抗HLADQDSA持续存在。没有不良事件与怀疑关系rATG，包括过敏反应，白细胞减少症或感染，观察在任何patient.Conclusions在这个小系列的患者，rATG出现一个有前途的治疗无反应的cAMR。进一步的评估，包括早期引入rATG，是必要的。
Background Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented.Methods Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg x 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib.Results The median time from diagnosis to cAMR was 179 days. rATG was started 5-741 days after diagnosis. Median estimated glomerular filtration rate (eGFR) increased from 40 mL/min/1.73 m(2) when rATG was started to 62 mL/min/1.73 m(2) 9 months later (p = 0.039). Four patients showed substantially higher eGFR after 9 months and 2 patients showed a small improvement; eGFR continued to decline in 3 patients after starting rATG. No grafts were lost during follow-up. At last follow-up, donor-specific antibodies (DSAs) were no longer detectable in 4 out of 8 patients for whom data were available, median fluorescence intensity had decreased substantially in 1 out of 8 patients; anti-HLADQDSAs persisted in 2 out of 8 patients. No adverse events with a suspected relation to rATG, including allergic reactions, leukocytopenia or infections, were observed in any of the patients.Conclusions In this small series of patients, rATG appears a promising treatment for unresponsive cAMR. Further evaluation, including earlier introduction of rATG, is warranted.