Background and Aims Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. Methods NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. Results Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13–0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94–7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. Conclusions In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

中文翻译：

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无机硝酸盐有益于治疗急性冠脉综合征冠状动脉造影后对比剂诱发的肾病：NITRATE-CIN 试验

背景和目的 造影剂肾病 (CIN)，也称为造影剂相关急性肾损伤 (CA-AKI)，是高危患者冠状动脉造影手术后发病率和死亡率的很大一部分原因，并且仍然是一个重大的未满足的需求。在临床前研究中，无机硝酸盐在体内化学还原为一氧化氮，具有肾脏保护作用，但这一观察结果尚未转化为临床。在这项研究中，报告了无机硝酸盐在预防急性冠脉综合征 (ACS) 高危患者中 CIN 的功效。方法 NITRATE-CIN 是一项双盲、随机、单中心、安慰剂对照试验，评估无机硝酸盐在 ACS 高危患者中预防 CIN 的功效。患者按 1:1 的比例随机分配至每天一次的硝酸钾（12 mmol）胶囊或安慰剂（氯化钾）胶囊，为期 5 天。主要终点是 CIN（KDIGO 标准）。次要结局包括 3 个月时的肾功能 [估计肾小球滤过率 (eGFR)]、手术性心肌梗死发生率和 12 个月时的主要不良心脏事件 (MACE)。本研究已在 ClinicalTrials.gov 注册：NCT03627130。结果 3 年多来，640 名患者被随机分配，中位随访时间为 1.0 年，其中 319 名患者接受无机硝酸盐治疗，321 名患者接受安慰剂治疗。试验参与者的平均年龄为 71.0 岁，其中 73.3% 为男性，75.2% 为白种人； 45.9% 患有糖尿病，56.0% 患有慢性肾病 (eGFR <60 mL/min)，人群的平均 Mehran 评分为 10。与安慰剂 (30.5%，P) 相比，无机硝酸盐治疗显着降低了 CIN 率 (9.1%) <.001)。在调整基线肌酐和糖尿病状态后，这种差异仍然存在（比值比 0.21，95% 置信区间 0.13-0.34）。无机硝酸盐的次要结局得到改善，手术性心肌梗塞发生率较低（2.7% vs. 12.5%，P = 0.003），改善 3 个月肾功能（组间 eGFR 变化为 5.17，95% CI 2.94–7.39） ）并与安慰剂相比降低了 1 年 MACE（9.1% 对比 18.1%，P = .001）。结论 在因 ACS 接受冠状动脉造影的有肾损伤风险的患者中，与安慰剂相比，每日一次的短程（5 天）无机硝酸盐可减少 CIN，改善 3 个月时的肾脏结局以及 1 年时的 MACE 事件。