Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Paris, France.
Am J Transplant. 2016 May;16(5):1596-603. doi: 10.1111/ajt.13663. Epub 2016 Mar 3.
Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR.
补体抑制剂在治疗急性抗体介导的排斥反应（ABMR）中尚未得到充分评估。我们进行了一项前瞻性、单臂试验研究，以探讨 C1 抑制剂（C1-INH）Berinert 联合大剂量静脉免疫球蛋白（IVIG）治疗常规治疗无效的急性 ABMR 的潜在效果和安全性。2013 年 4 月至 2014 年 7 月期间，纳入对常规治疗无反应的活动期 ABMR 和急性移植物功能障碍的肾移植受者，并接受 C1-INH 和 IVIG 治疗 6 个月（6 例）。主要终点是纳入后 6 个月（M+6）时 eGFR 的变化。次要终点包括 M+6 时组织学和 DSA 特征的变化以及评估的不良事件。所有患者在纳入和 M+6 之间 eGFR 均有所改善：从 38.7 ± 17.9 至 45.2 ± 21.3 mL/min/1.73 m(2)（p = 0.0277）。组织学特征无变化，除 C4d 沉积率从 5/6 降至 1/6（p = 0.0455）。DSA C1q 状态从 6/6 变为 1/6 阳性（p = 0.0253）。观察到 1 例深静脉血栓形成。在二次分析中，将 C1-INH 患者与类似的历史对照组（21 例）进行比较。C1-INH 联合 IVIG 治疗是安全的，可改善对常规治疗无反应的急性 ABMR 肾移植受者的移植物功能。
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