目的:在肾病综合征(NS)的啮齿动物模型中,阿米洛利阻断上皮钠通道ENaC可防止水肿形成.然而,除了病例报告,对于NS患者,没有证据支持ENaC阻断.
方法:单中心随机对照AMILOR研究调查了阿米洛利的抗水肿作用(起始剂量5毫克/天,max.15mg/天)与使用loop利尿剂呋塞米的标准治疗(40mg/天,max.120毫克/天)超过16天。通过生物阻抗光谱法(BCM,费森尤斯)。根据OH的反应,在第2、5、8和12天调整利尿剂剂量,如有必要,从d8开始添加氢氯噻嗪(HCT)(12.5mg/天,max.25毫克/天)。主要终点是在d8时OH的减少。由于招募不足和实际效应大小低的统计能力低,该研究被提前终止。
结果:在阿米洛利臂中,基线OH的中位数为26.4(四分位距15.5-35.1)%细胞外水(ECW),在呋塞米臂中为27.9(24.1-29.4)%ECW,8天后降低了1.95(0.80-6.40)和5.15(0.90-8.30)%ECW,分别,16天后10.10(1.30-14.40)和7.40(2.80-10.10)%ECW,分别。在d8和d16的OH降低在两个臂之间没有显著差异。
结论:AMILOR研究是第一个随机对照试验研究,表明与呋塞米具有相似的抗水肿作用。需要进一步的研究来更好地确定阿米洛利在NS中的作用(EudraCT2019-002607-18)。
OBJECTIVE: In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with
amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS.
METHODS: The monocentric randomized controlled AMILOR study investigated the antiedematous effect of
amiloride (starting dose 5 mg/day, max. 15 mg/day) in comparison to standard therapy with the loop diuretic furosemide (40 mg/day, max. 120 mg/day) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (BCM, Fresenius). Depending on the OH response, diuretic dose was adjusted on days 2, 5, 8 and 12, and if necessary, hydrochlorothiazide (HCT) was added from d8 (12.5 mg/day, max. 25 mg/day). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and a low statistical power due to a low actual effect size.
RESULTS: Median baseline OH was +26.4 (interquartile range 15.5-35.1)% extracellular water (ECW) in the
amiloride arm and + 27.9 (24.1-29.4)% ECW in the furosemide arm and decreased by 1.95 (0.80-6.40) and 5.15 (0.90-8.30)% ECW after 8 days, respectively, and by 10.10 (1.30-14.40) and 7.40 (2.80-10.10)% ECW after 16 days, respectively. OH decrease on d8 and d16 was not significantly different between both arms.
CONCLUSIONS: The AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Further studies are required to better define the role of
amiloride in NS (EudraCT 2019-002607-18).