Background:Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis.Methods:In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7–15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters.Results:Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (−79.6%; P<0.001), hs-CRP (−46.5%; P<0.001), IL-6 (−27.1%; P<0.001), and TNF-α (−51.7%; P<0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences −12.0 [95% CI −18.0 to −9.5] and −9.0 [95% CI −12.0 to −4.5]; P<0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed.Conclusions:Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04582097.

中文翻译：

---

雷米普利对维持性血液透析高血压儿童内皮功能障碍和炎症的生物标志物的影响：SEARCH 随机安慰剂对照试验

背景：高血压、内皮功能障碍和炎症与终末期肾病的心血管死亡率增加有关。我们评估了 ACE（血管紧张素转换酶）抑制对维持性血液透析的终末期肾病高血压儿童内皮功能障碍和炎症的生物标志物的影响。方法：在一项随机、双盲、安慰剂对照试验中，135 ( 72 名男性/63 名女性）儿童和青少年（7-15 岁）被随机分配接受 2.5 mg 每天一次的雷米普利（n=68）或安慰剂（n=67）治疗 16 周。主要结果是不对称二甲基精氨酸（内皮功能障碍的标志物）和 hs-CRP（高敏 C 反应蛋白）（炎症标志物）的血清浓度。IL-6 (interleukin-6) 的变化，TNF-α（肿瘤坏死因子-α）、收缩压（S）和舒张压（D）是次要结局。钾水平的变化和高钾血症的发生率属于安全性参数。结果：雷米普利（而非安慰剂）显着降低了不对称二甲基精氨酸的血清水平（-79.6%；P <0.001)、hs-CRP (-46.5%; P <0.001)、IL-6 (-27.1%; P <0.001) 和 TNF-α (-51.7%; P <0.001)。两组的收缩压和舒张压均显着降低，接受雷米普利的儿童降幅更大（组间中位数差异 -12.0 [95% CI -18.0 至 -9.5] 和 -9.0 [95% CI -12.0 至 - 4.5]; P<0.001，分别）。雷米普利组中不对称二甲基精氨酸、hs-CRP、IL-6 或 TNF-α 的变化与血压降低没有显着相关性。没有观察到严重的高钾血症或其他与治疗相关的严重不良事件。结论：雷米普利改善了维持性血液透析高血压儿童内皮功能障碍和炎症的生物标志物，并具有降低血压的有效和安全潜力。注册：网址：https ://www.clinicaltrials.gov；唯一标识符：NCT04582097。