Amiloride vs. furosemide for the treatment of edema in human nephrotic syndrome: a pilot study (AMILOR)

Abstract

Abstract In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/d, max. 15 mg/d) in nephrotic patients in comparison to standard therapy with the loop diuretic furosemide (40 mg/d, max. 120 mg/d) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (Body Composition Monitor, 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 (start 12.5 mg/d, max. 25 mg/d). 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. 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. In conclusion, the AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Thus, amiloride emerges as an alternative to the standard therapy with furosemide.