Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany.
Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Pediatr Nephrol. 2017 Nov;32(11):2133-2142. doi: 10.1007/s00467-017-3725-1. Epub 2017 Jul 17.
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.
Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 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.
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 when rATG was started to 62 mL/min/1.73 m 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-HLA DQ DSAs 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.
In this small series of patients, rATG appears a promising treatment for unresponsive cAMR. Further evaluation, including earlier introduction of rATG, is warranted.
慢性抗体介导的排斥反应(cAMR)是导致晚期肾移植失败的主要原因,但目前的治疗方法往往效果不佳。兔抗人胸腺细胞免疫球蛋白(rATG)可能有帮助,但实际上其应用尚未被记录。
我们对 9 名儿童肾移植患者进行了回顾性数据分析,这些患者在我们中心接受了 rATG(1.5mg/kg×5 天)治疗,这些患者在对脉冲泼尼松、静脉注射免疫球蛋白、利妥昔单抗和增加免疫抑制强度(包括在某些情况下切换至巴利昔单抗)无反应后出现 cAMR。有些患者还联合使用硼替佐米。
从诊断到 cAMR 的中位时间为 179 天。rATG 在诊断后 5-741 天开始使用。rATG 开始时的中位估算肾小球滤过率(eGFR)为 40mL/min/1.73m,9 个月后增加至 62mL/min/1.73m(p=0.039)。4 名患者在 9 个月后 eGFR 显著升高,2 名患者略有改善;3 名患者在开始 rATG 后 eGFR 持续下降。在随访期间没有移植肾丢失。在最后一次随访时,8 名患者中有 4 名患者的供体特异性抗体(DSA)已不可检测,8 名患者中有 1 名患者的中位荧光强度显著降低;8 名患者中有 2 名患者的抗 HLA-DQ DSA 持续存在。在任何患者中均未观察到与 rATG 相关的可疑不良反应,包括过敏反应、白细胞减少或感染。
在本小系列患者中,rATG 似乎是治疗无反应性 cAMR 的一种有前途的治疗方法。需要进一步评估,包括更早引入 rATG。