Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation
Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation
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DOI：
10.1016/j.transproceed.2019.02.051
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发表时间：
2019-10-01
影响因子：
0.9
通讯作者：
Yagisawa, Takashi
中科院分区：
文献类型：
--
作者：
Nanmoku, Koji;Shinzato, Takahiro;Yagisawa, Takashi
背景兔抗胸腺细胞球蛋白（rATG）诱导与新生供体特异性抗体（DSA）和抗体介导的排斥反应（AMR）的发生率降低相关。因此，rATG给药被认为是AMR的治疗方法。然而，只有少数研究研究了肾移植后rATG治疗AMR。在2013年4月至2018年3月期间，连续进行了162例从头肾移植，诱导免疫抑制治疗包括他克莫司，吗替麦考酚酯，甲泼尼龙和巴利昔单抗。AMR的诊断基于DSA和发作活检结果。对于DSA阳性受体，在rATG给药（1.5 mg/kg，持续5天）之前进行血浆置换以去除DSA。回顾性分析了接受rATG治疗的患者的移植物功能。共有13名肾移植受者在移植后302天内发生了活动性AMR。rATG给药后，平均血清肌酐和尿蛋白水平分别在46天内从3.03 mg/dL显著下降至1.68 mg/dL（P = .002），在106天内从3.01 g/gCr显著下降至0.54 g/gCr（P = .006）。rATG给药后外周血淋巴细胞计数迅速下降，并在12个月内保持较低水平。不良事件中，发热（84.6%）、巨细胞病毒血症（84.6%）、血小板减少（61.5%）、贫血（30.8%）和中性粒细胞减少（15.4%）发生在rATG给药后3个月内。rATG通过抑制活动性AMR肾移植受者的外周血淋巴细胞来改善移植物功能。rATG给药作为活动性AMR的治疗可能有助于肾移植后的积极移植结局。
Background. Rabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation.Methods. Between April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function.Results. A total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration.Conclusions. rATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.