BACKGROUND Distal diuretics are considered less effective than loop diuretics in CKD. However, data to support this perception are limited. METHODS 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. RESULTS A total of 26 patients (with a mean eGFR of 39 ml/min per 1.73 m2) 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 β2-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. CONCLUSIONS 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. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease (DD), NCT02875886.

中文翻译：

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慢性肾脏病高血压患者远端利尿剂与饮食钠盐限制的随机对照试验。

背景技术在CKD中，远端利尿剂被认为不如loop利尿剂有效。但是，支持这种看法的数据是有限的。方法为了研究在CKD G3或G4期并伴有高血压的患者中远端利尿剂在降低BP方面是否不低于饮食钠盐限制，我们进行了一项为期6周的随机，开放标签交叉试验，比较了阿米洛利/氢氯噻嗪（5 mg / 50 mg每天），并限制饮食中的钠（每天60 mmol）。在随机分组之前，抗高血压药物已停药2周。我们分析了对血压，肾脏功能和体液平衡的影响，并将其与利尿剂的肾脏清除率相关。结果共有26例患者（平均eGFR为39 ml / min / 1.73 m2）完成了两种治疗。饮食中的钠限制将钠排泄从每天160减少到64 mmol。与钠盐限制（134至129 mm Hg）相比，利尿剂的24小时收缩压（SBP；从138至124 mm Hg）降低更大，并且对细胞外水，eGFR，血浆肾素，和醛固酮。两种干预措施均导致体重和NT-proBNP下降相似。两种方法都不能显着降低白蛋白尿，而利尿剂却不能显着降低尿血管紧张素原和β2-微球蛋白排泄。尽管较低的eGFR和较高的血浆吲哚酚硫酸盐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得以维持。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，并且四名患者出现轻度低钠血症。结论远端利尿剂在降低CKD的BP和细胞外容量方面不逊于饮食钠盐限制。尽管利尿剂清除率较低，但仍可维持CKD的利尿剂敏感性。临床试验注册名称和注册号DD研究：慢性肾脏病（DD）中盐敏感性的饮食或利尿剂，NCT02875886。