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Kidney Week

Abstract: TH-PO399

Amiloride vs. Furosemide for the Treatment of Edema in Nephrotic Syndrome (AMILOR): A Pilot Study

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Artunc, Ferruh, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tubingen, Baden-Württemberg, Germany
  • Vogel, Elisabeth, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tubingen, Baden-Württemberg, Germany
  • Bohnert, Bernhard N., Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tubingen, Baden-Württemberg, Germany
  • Essigke, Daniel, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tubingen, Baden-Württemberg, Germany
  • Schork, Anja, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tubingen, Baden-Württemberg, Germany
Background

According to findings from nephrotic mouse models, edema formation in nephrotic syndrome (NS) is caused by sodium retention through activation of the epithelial sodium channel ENaC. In these models, edema formation could be prevented by ENaC blockade with amiloride. The monocentric randomized controlled AMILOR study investigated the anti-edematous effect of the ENaC blocker amiloride in nephrotic patients in comparison to standard therapy with the loop diuretic furosemide.

Methods

Patients with acute NS (n=10 per arm, etiology MCD n=6, MN n=8, FSGS n=2, amyloidosis n=1, IgAN n=1, other n=2; age 53 [interquartile range 38–61], male/female 13/7) and eGFR (CKD-EPI)>30 ml/min/1,73m2 were randomized to treatment with amiloride (start 5mg/d, max.15mg/d) or furosemide (40mg/d, max.120mg/d) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (Body Composition Monitor, Fresenius). Depending on the course of OH, the dose was adjusted on days 2,5,8,12 and 16 and, if necessary, HCT was added on d8 (start 12.5mg/d, max. 25mg/d). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and low statistical power due to a low actual effect size.

Results

Median baseline OH was 5.3 L /1.73m2 (26 [18-34]% of extracellular water [ECW]) in the amiloride arm and 6.2 L/1.73m2 (28 [24-29]% ECW) in the furosemide arm. On d8, OH decreased to 3.7 L/1.73m2 (19 [16-27]% ECW) in the amiloride arm and to 4.5L/1.73m2 (21 [13-28]% ECW) in the furosemide arm. Till d16, OH decreased significantly to 60 [29-93]% or 2.2 L/1.73m2 (12 [9-24]% ECW) in the amiloride arm and to 69 [57-85]% or 3.4 L/1.73m2 (17 [14-27]% ECW) in the furosemide arm. The decrease in OH on d8 and d16 was not significantly different between both arms. Hyperkalemia>5.3 mM (max. 5.7 mM) occurred in n=3 patients taking amiloride (all GFR according to CKD-EPI-Cys <40mL/min/1.73m2).

Conclusion

The AMILOR study is the first randomized controlled pilot study on the use of diuretics in NS demonstrating an antiedematous effect of the ENaC blocker amiloride without a significant difference to furosemide. Thus, amiloride emerges as an alternative to the standard therapy with furosemide. The knowledge gained lays the foundation for the design of a larger multi-centre study with greater statistical power.