Divisions of Nephrology and Transplantation.
Dietetics, and.
J Am Soc Nephrol. 2020 Mar;31(3):650-662. doi: 10.1681/ASN.2019090905. Epub 2020 Jan 29.
Distal diuretics are considered less effective than loop diuretics in CKD. However, data to support this perception are limited.
To investigate whether distal diuretics are noninferior to dietary sodium restriction in reducing BP in patients with CKD stage G3 or G4 and hypertension, we conducted a 6-week, randomized, open-label crossover trial comparing amiloride/hydrochlorothiazide (5 mg/50 mg daily) with dietary sodium restriction (60 mmol per day). Antihypertension medication was discontinued for a 2-week period before randomization. We analyzed effects on BP, kidney function, and fluid balance and related this to renal clearance of diuretics.
A total of 26 patients (with a mean eGFR of 39 ml/min per 1.73 m) completed both treatments. Dietary sodium restriction reduced sodium excretion from 160 to 64 mmol per day. Diuretics produced a greater reduction in 24-hour systolic BP (SBP; from 138 to 124 mm Hg) compared with sodium restriction (from 134 to 129 mm Hg), as well as a significantly greater effect on extracellular water, eGFR, plasma renin, and aldosterone. Both interventions resulted in a similar decrease in body weight and NT-proBNP. Neither approaches decreased albuminuria significantly, whereas diuretics did significantly reduce urinary angiotensinogen and 2-microglobulin excretion. Although lower eGFR and higher plasma indoxyl sulfate correlated with lower diuretic clearance, the diuretic effects on body weight and BP at lower eGFR were maintained. During diuretic treatment, higher PGE2 excretion correlated with lower free water clearance, and four patients developed mild hyponatremia.
Distal diuretics are noninferior to dietary sodium restriction in reducing BP and extracellular volume in CKD. Diuretic sensitivity in CKD is maintained despite lower diuretic clearance.
DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease (DD), NCT02875886.
在慢性肾脏病（CKD）患者中，远曲利尿剂的效果不如袢利尿剂。然而，支持这一观点的数据有限。
为了研究远曲利尿剂是否不如饮食钠限制在降低 CKD 3 或 4 期和高血压患者的血压方面更有效，我们进行了一项为期 6 周的、随机、开放标签的交叉试验，比较了阿米洛利/氢氯噻嗪（5 毫克/50 毫克每日）与饮食钠限制（每天 60 毫摩尔）。在随机分组前，抗高血压药物停用 2 周。我们分析了对血压、肾功能和液体平衡的影响，并将其与利尿剂的肾清除率相关联。
共有 26 名患者（平均 eGFR 为 39ml/min/1.73m）完成了两种治疗。饮食钠限制使钠排泄从 160 毫摩尔/天减少到 64 毫摩尔/天。与钠限制（从 134 减少到 129mmHg）相比，利尿剂对 24 小时收缩压（SBP）的降低更大（从 138 减少到 124mmHg），对细胞外液、eGFR、血浆肾素和醛固酮的影响也更大。两种干预措施均使体重和 NT-proBNP 显著下降。两种方法均未显著减少白蛋白尿，而利尿剂显著减少尿血管紧张素原和 2-微球蛋白排泄。虽然较低的 eGFR 和较高的血浆吲哚硫酸酯与较低的利尿剂清除率相关，但在较低的 eGFR 下，利尿剂对体重和血压的作用仍然存在。在利尿剂治疗期间，较高的 PGE2 排泄与较低的游离水清除率相关，有 4 名患者出现轻度低钠血症。
在降低 CKD 患者的血压和细胞外容量方面，远曲利尿剂与饮食钠限制效果相当。尽管利尿剂清除率降低，但 CKD 患者的利尿剂敏感性仍然保持。
DD 研究：慢性肾脏病中盐敏感性的饮食或利尿剂（DD），NCT02875886。
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