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

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.

Renal, ocular, and neuromuscular involvements in patients with CLDN19 mutations.

BACKGROUND AND OBJECTIVES: The objective of this study was to describe the renal and extrarenal findings in patients with recessively inherited familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) associated with CLDN19 mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medical records of three patients from two French unrelated families with CLDN19 mutations were retrospectively examined. RESULTS: Direct sequencing of CLDN19 identified a known variant (p.Gly20Asp) in all patients and a new missense mutation (p.Val44Met) in one (compound heterozygous). The patients' renal phenotype closely mimicked CLDN16-related nephropathy: low serum Mg2+ (<0.65 mmol/L) despite oral supplementation, hypercalciuria partly thiazide-sensitive, and progressive renal decline with ESRD reached at age 16 and 22 years in two individuals. Primary characteristics (failure to thrive, recurrent urinary tract infections, or abdominal pain), age at onset (0.8 to 16 years), and rate of renal decline were highly heterogeneous. Ocular involvement was identified in all patients, although two patients did not have visual loss. Additionally, exercise intolerance with pain, weakness, and electromyographical alterations mimicking a Ca2+/K+ channelopathy (pattern V) were observed in two of three individuals. These features persisted despite the normalization of serum K+ and Mg2+ after renal transplantation. CONCLUSIONS: Ocular manifestations, even subtle, and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that need to be searched for in patients with FHHNC and may indicate CLDN19 mutations.