Amiloride versus furosemide for the treatment of edema in patients with nephrotic syndrome: A pilot study (AMILOR)
- PMID: 38822593
- DOI: 10.1111/apha.14183
Amiloride versus furosemide for the treatment of edema in patients with nephrotic syndrome: A pilot study (AMILOR)
Abstract
Aim: 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.
Conclusion: 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).
Keywords: amiloride; edema; epithelial sodium channels; furosemide; nephrotic syndrome.
© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.
References
REFERENCES
-
- Bockenhauer D. Over‐ or underfill: not all nephrotic states are created equal. Pediatr Nephrol. 2013;28(8):1153‐1156.
-
- Artunc F, Worn M, Schork A, Bohnert BN. Proteasuria‐the impact of active urinary proteases on sodium retention in nephrotic syndrome. Acta Physiol (Oxf). 2019;225(4):e13249.
-
- Xiao M, Bohnert BN, Grahammer F, Artunc F. Rodent models to study sodium retention in experimental nephrotic syndrome. Acta Physiol (Oxf). 2022;235(3):e13844.
-
- Bohnert BN, Daiminger S, Worn M, et al. Urokinase‐type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)‐mediated sodium retention in experimental nephrotic syndrome. Acta Physiol (Oxf). 2019;227(4):e13286.
-
- Bohnert BN, Essigke D, Janessa A, et al. Experimental nephrotic syndrome leads to proteolytic activation of the epithelial Na(+) channel in the mouse kidney. Am J Physiol Renal Physiol. 2021;321(4):F480‐f493.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous