Objectives

This study sought to determine the efficacy profile and safety of recombinant human C1 esterase inhibitor (rhC1INH) in the prevention of contrast-associated acute kidney injury after elective coronary angiography.

Background

Contrast-associated acute kidney injury is caused by tubular cytotoxicity and ischemia/reperfusion injury. RhC1INH is effective in reducing renal ischemia/reperfusion injury in experimental models.

Methods

In this placebo-controlled, double-blind, single-center trial 77 patients with chronic kidney disease were randomized to receive 50 IU/kg rhC1INH before and 4 h after elective coronary angiography or placebo. The primary outcome was the peak change of urinary neutrophil gelatinase-associated lipocalin within 48 h, a surrogate marker of kidney injury.

Results

Median peak change of urinary neutrophil gelatinase-associated lipocalin was lower in the rhC1INH group (4.7 ng/ml vs. 22.5 ng/ml; p = 0.038) in the per-protocol population but not in the modified intention-to-treat analysis, and in patients with percutaneous coronary interventions (median, 1.8 ng/ml vs. 26.2 ng/ml; p = 0.039 corresponding to a median proportion peak change of 11% vs. 205%; p = 0.002). The incidence of a cystatin C increase ≥10% within 24 h was lower in the rhC1INH group (16% vs. 33%; p = 0.045), whereas the frequency of contrast-associated acute kidney injury was comparable. Adverse events during a 3-month follow-up were similarly distributed.

Conclusions

Administration of rhC1INH before coronary angiography may attenuate renal injury as reflected by urinary neutrophil gelatinase-associated lipocalin and cystatin C. The safety profile of rhC1INH was favorable in a patient population with multiple comorbidities. (Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects [PROTECT]; NCT02869347).

中文翻译：

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重组人C1-酯酶抑制剂预防造影剂肾脏损伤的随机试验

目标

这项研究试图确定重组人C1酯酶抑制剂（rhC1INH）在预防性冠状动脉造影后预防与造影剂相关的急性肾脏损伤中的功效和安全性。

背景

造影剂相关的急性肾损伤是由肾小管细胞毒性和缺血/再灌注损伤引起的。在实验模型中，RhC1INH可有效减少肾脏缺血/再灌注损伤。

方法

在这项安慰剂对照，双盲，单中心试验中，将77例慢性肾脏病患者随机分配至择期冠状动脉造影或安慰剂治疗前后4 h接受50 IU / kg rhC1INH。主要结局是在48小时内尿中性粒细胞明胶酶相关脂质运载蛋白的峰值变化，这是肾脏损伤的替代指标。

结果

在每协议人群中，rhC1INH组中尿中性粒细胞明胶酶相关脂钙蛋白的峰值中位数较低（4.7 ng / ml与22.5 ng / ml； p = 0.038），但在改良的意向性治疗分析中则没有，以及经皮冠状动脉介入治疗的患者（中位数为1.8 ng / ml对26.2 ng / ml； p = 0.039，对应于中位比例峰值变化为11％对205％； p = 0.002）。在rhC1INH组中，胱抑素C在24小时内增加≥10％的发生率较低（16％对33％； p = 0.045），而与造影剂相关的急性肾损伤的发生率却相当。在3个月的随访期间，不良事件的分布也相似。

结论

冠状动脉造影之前给予rhC1INH可能会减轻肾损伤，如尿中性粒细胞明胶酶相关的lipocalin和cystatin C所反映。rhC1INH的安全性在患有多种合并症的患者中是有利的。（重组人C1酯酶抑制剂在高风险受试者中预防造影剂诱发的肾病的预防[保护]； NCT02869347）。