c kidney disease randomized trial demonstrated a robust reduction in systolic BP in stage 4 CKD. In this study, we explore the mechanisms underlying the antihypertensive effect of CTD. Methods In this prespecified analysis, we analyzed the contributions of baseline levels of 24-hour urinary sodium and aldosterone and the changes from baseline to 4 weeks in the multiple mediators reflecting volume status in a causal mediation analysis framework. Baseline levels of these mediators served as covariates. No power calculation for this analysis was performed. Results Of the 160 patients randomized, 140 (87.5%) were included in this analysis. Compared with placebo, CTD within 4 weeks reduced weight −1.5% (95% confidence interval [CI], −2.2 to −0.7) and volume −1.4% (95% CI, −2.2 to −0.6), stimulated plasma renin 40.5% (95% CI, 25.4% to 57.4%) and serum aldosterone 40.2% (95% CI, 11.7% to 76%), and reduced plasma N-terminal pro-B-type natriuretic peptide levels −19.4% (95% CI, −33.8% to −1.9%). Mediation analysis revealed the following results: for weight change, the total effect on systolic BP was −10.8 mm Hg (95% CI, −16 to −5.7), of which weight change (indirect effect) accounted for −0.9 mm Hg (95% CI, −4.2 to 2.5) and BP change independent of weight (direct effect) accounted for −10 mm Hg (−15.7 to −4.2). Thus, the percent mediation was 8.1% (95% CI, −22.4 to 38.5). Baseline excretion of 24-hour sodium or aldosterone or any of the changes in the above mediators examined accounted for <2 mm Hg BP drop and were not significant for any of the mediators. Conclusions CTD improved BP control among patients with advanced CKD independent of baseline urinary sodium, aldosterone, weight loss, or changes in the renin-angiotensin system or N-terminal pro-B-type natriuretic peptide. Clinical Trial registry name and registration number: CTD in chronic kidney disease ClinicalTrials.gov number: NCT02841280....

中文翻译：

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氯噻酮治疗晚期慢性肾病的降压作用机制：因果中介分析


c 肾脏疾病随机试验表明，4 期 CKD 的收缩压显着降低。在这项研究中，我们探讨了 CTD 抗高血压作用的机制。方法 在这个预先指定的分析中，我们在因果中介分析框架中分析了 24 小时尿钠和醛固酮基线水平的贡献，以及反映容量状态的多个中介从基线到 4 周的变化。这些中介的基线水平作为协变量。该分析未进行功效计算。结果 在随机分组的 160 名患者中，140 名 (87.5%) 被纳入本次分析。与安慰剂相比，CTD 在 4 周内减少了体重 -1.5%（95% 置信区间 [CI]，-2.2 至 -0.7）和体积 -1.4%（95% CI，-2.2 至 -0.6），刺激血浆肾素减少 40.5% （95% CI，25.4% 至 57.4%）和血清醛固酮 40.2%（95% CI，11.7% 至 76%），血浆 N 端 B 型利钠肽前体水平降低 -19.4%（95% CI， −33.8％至-1.9％）。中介分析揭示了以下结果：对于体重变化，对收缩压的总影响为-10.8 mm Hg（95% CI，-16至-5.7），其中体重变化（间接影响）占-0.9 mm Hg（95 % CI，-4.2至2.5）和与体重无关的血压变化（直接影响）占-10毫米汞柱（-15.7至-4.2）。因此，中介百分比为 8.1%（95% CI，-22.4 至 38.5）。 24 小时钠或醛固酮的基线排泄或上述检查介质的任何变化导致血压下降 <2 mm Hg，并且对于任何介质都不显着。结论 CTD 可改善晚期 CKD 患者的血压控制，与基线尿钠、醛固酮、体重减轻或肾素-血管紧张素系统或 N 末端 B 型利钠肽前体的变化无关。 临床试验注册名称和注册号：慢性肾脏病 CTD ClinicalTrials.gov 编号：NCT02841280....