Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation.
Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation.
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DOI：
10.1097/tp.0000000000003255
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发表时间：
2021-02-01
期刊：
影响因子：
6.2
通讯作者：
Cooper M
中科院分区：
文献类型：
--
作者：
Bromberg JS;Weir MR;Gaber AO;Yamin MA;Goldberg ID;Mayne TJ;Cal W;Cooper M
补充数字内容可在文本中找到。接受肾移植的患者（20%-50%）经历急性肾损伤，导致移植物功能延迟。ANG-3777是一种与c-MET受体结合的肝细胞生长因子模拟物。在动物模型中，ANG-3777减少细胞凋亡，增加增殖，促进器官修复和功能。这是一项随机、双盲、安慰剂对照的2期试验，患者接受肾移植，移植后前24小时内连续8小时尿量<50 cc/h，或移植前至移植后24小时肌酐降低率<30%。受试者以2：1至3的比例随机分配，每日一次IV输注ANG-3777 2 mg/kg（n = 19）或安慰剂（n = 9）。主要终点：达到24小时尿液≥1200 cc的时间（天）。接受ANG-3777治疗的患者更有可能在移植后28天达到主要终点，即24小时尿量1200 cc（83.3% vs 50%安慰剂;对数秩检验：χ2 = 2.799，P = 0.09）。与安慰剂组相比，ANG-3777组患者的尿量增加幅度较大;血清肌酐较低; C反应蛋白和中性粒细胞明胶酶相关脂质运载蛋白降低幅度较大;透析次数较少，透析持续时间较短;住院天数较少;移植物衰竭显著较少;估计肾小球滤过率较高。两组中不良事件发生的受试者百分比相似。与安慰剂相比，ANG-3777治疗受试者的肾功能改善的有效性信号，具有良好的安全性特征。
Supplemental Digital Content is available in the text. Patients (20%–50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours. Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm. There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.