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兔抗胸腺细胞球蛋白对肾移植后急性和慢性活动性抗体介导排斥反应的影响

Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation.

作者信息

Nanmoku Koji, Shinzato Takahiro, Kubo Taro, Shimizu Toshihiro, Yagisawa Takashi

机构信息

Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, Shimotsuke, Japan.

Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, Shimotsuke, Japan.

出版信息

Transplant Proc. 2019 Oct;51(8):2602-2605. doi: 10.1016/j.transproceed.2019.02.051. Epub 2019 Jul 16.

Abstract

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.

摘要

背景

兔抗胸腺细胞球蛋白(rATG)诱导治疗与新发供者特异性抗体(DSA)的发生率降低及抗体介导的排斥反应(AMR)相关。因此,rATG给药被视为AMR的一种治疗方法。然而,仅有少数研究探讨了肾移植后使用rATG治疗AMR的情况。

方法

在2013年4月至2018年3月期间,连续进行了162例初次肾移植手术,诱导免疫抑制治疗包括他克莫司、霉酚酸酯、甲泼尼龙和巴利昔单抗。根据DSA的存在及移植肾活检结果诊断AMR。对于DSA阳性受者,在给予rATG(1.5mg/kg,共5天)之前进行血浆置换以清除DSA。对接受rATG治疗活动性AMR的患者的移植肾功能进行回顾性分析。

结果

共有13例肾移植受者在移植后302天内发生活动性AMR。给予rATG后,血清肌酐均值和尿蛋白水平分别在46天内从3.03mg/dL显著降至1.68mg/dL(P = 0.002),在106天内从3.01g/gCr降至0.54g/gCr(P = 0.006)。给予rATG后外周血淋巴细胞计数迅速下降,并在12个月内维持在较低水平。关于不良事件,rATG给药后3个月内发生发热(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%)。

结论

rATG通过抑制活动性AMR的肾移植受者外周血淋巴细胞来改善移植肾功能。rATG给药作为活动性AMR的一种治疗方法可能有助于肾移植后获得良好的移植结局。

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