内皮功能障碍在CKD患者中很常见。我们测试了亚硝酸钠和异槲皮素联合治疗对CKD患者内皮功能障碍生物标志物的疗效和安全性。
这是随机的,双盲,安慰剂对照2期试验纳入70例透析前CKD患者.35人被随机分配到亚硝酸钠(40毫克,每天两次)和异槲皮素(225毫克,每天一次)的联合治疗12周,35人被随机分配到安慰剂组.主要结果是12周干预期间血流介导的血管舒张的平均变化。次要和安全性结果包括内皮功能障碍的生物标志物,炎症,和氧化应激以及肾功能,高铁血红蛋白,和不良事件。进行了意向治疗分析。
基线特征,包括年龄,性别,种族,吸烟,高血压和糖尿病史,使用肾素-血管紧张素系统阻滞剂,BP,空腹血糖,血脂谱,肾功能,尿白蛋白-肌酐比值,和内皮生物标志物,组间具有可比性。在为期12周的干预中,血流介导的血管舒张增加1.1%(95%置信区间,治疗组的-0.1至2.3)和0.3%(95%置信区间,-0.9至1.5)在安慰剂组中,净变化为0.8%(95%置信区间,-0.9至2.5)。此外,内皮功能障碍的生物标志物的变化(血管粘附分子-1,细胞间粘附分子-1,E-选择素,vWf,内皮抑素,和不对称二甲基精氨酸),炎症(TNF-α,IL-6,C反应蛋白,IL-1受体拮抗剂,和单核细胞趋化蛋白-1),和氧化应激(氧化LDL和硝基酪氨酸)两组之间没有显着差异。此外,eGFR的变化,尿白蛋白-肌酐比值,高铁血红蛋白,两组间不良事件无显著差异.
这项随机2期初步试验表明,在CKD患者中,与安慰剂相比,亚硝酸钠和异槲皮素联合治疗不能显著改善血流介导的血管舒张或其他内皮功能生物标志物,但也不会增加不良事件。
亚硝酸盐,异槲皮素,和内皮功能障碍(NICE),NCT02552888。
Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD.
This randomized, double-blind, placebo-controlled phase 2 pilot
trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted.
Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups.
This randomized phase 2 pilot
trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD.
Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.