Indomethacin, amiloride, or eplerenone for treating hypokalemia in Gitelman syndrome.

Abstract

Patients with Gitelman syndrome (GS), an inherited salt-losing tubulopathy, are usually treated with potassium-sparing diuretics or nonsteroidal anti-inflammatory drugs and oral potassium and magnesium supplementations. However, evidence supporting these treatment options is limited to case series studies. We designed an open-label, randomized, crossover study with blind end point evaluation to compare the efficacy and safety of 6-week treatments with one time daily 75 mg slow-release indomethacin, 150 mg eplerenone, or 20 mg amiloride added to constant potassium and magnesium supplementation in 30 patients with GS (individual participation: 48 weeks). Baseline plasma potassium concentration was 2.8±0.4 mmol/L and increased by 0.38 mmol/L (95% confidence interval [95% CI], 0.23 to 0.53; P<0.001) with indomethacin, 0.15 mmol/L (95% CI, 0.02 to 0.29; P=0.03) with eplerenone, and 0.19 mmol/L (95% CI, 0.05 to 0.33; P<0.01) with amiloride. Fifteen patients became normokalemic: six with indomethacin, three with eplerenone, and six with amiloride. Indomethacin significantly reduced eGFR and plasma renin concentration. Eplerenone and amiloride each increased plasma aldosterone by 3-fold and renin concentration slightly but did not significantly change eGFR. BP did not significantly change. Eight patients discontinued treatment early because of gastrointestinal intolerance to indomethacin (six patients) and hypotension with eplerenone (two patients). In conclusion, each drug increases plasma potassium concentration in patients with GS. Indomethacin was the most effective but can cause gastrointestinal intolerance and decreased eGFR. Amiloride and eplerenone have similar but lower efficacies and increase sodium depletion. The benefit/risk ratio of each drug should be carefully evaluated for each patient.

• Authors: Anne Blanchard, Rosa Vargas-Poussou, Marion Vallet, Aurore Caumont-Prim, Julien Allard, Estelle Desport, Laurence Dubourg, Matthieu Monge, Damien Bergerot, Stéphanie Baron, Marie Essig, Frank Bridoux, Ivan Tack, Michel Azizi
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 26 Issue 2 Pg. 468-75 (Feb 2015) ISSN: 1533-3450 [Electronic] United States
• PMID: 25012174 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by the American Society of Nephrology.

Chemical References

• Spironolactone
• Eplerenone
• Amiloride
• Renin
• Potassium
• Indomethacin

Topics

• Adolescent
• Adult
• Amiloride (adverse effects, pharmacology, therapeutic use)
• Blood Pressure (drug effects, physiology)
• Body Weight (drug effects, physiology)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Eplerenone
• Female
• Gitelman Syndrome (complications, metabolism, physiopathology)
• Glomerular Filtration Rate (drug effects, physiology)
• Heart Rate (drug effects, physiology)
• Humans
• Hypokalemia (drug therapy, etiology, physiopathology)
• Indomethacin (adverse effects, pharmacology, therapeutic use)
• Male
• Middle Aged
• Potassium (blood)
• Renin (blood)
• Spironolactone (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Treatment Outcome
• Young Adult