Effect of Hydrochlorothiazide on Urinary Calcium Excretion in Dent Disease: An Uncontrolled Trial

hyponatremiaBackground: Thiazide doses equivalent to 1 to 2 mg/kg/d of hydrochlorothiazicle (HCTZ) have been proposed to correct hypercalciuria and prevent kidney failure in patients with Dent disease. However, they can cause adverse metabolic effects in the long term. In treating hypertension in children, lower thiazide doses have been shown to be as effective and well tolerated. Study Design: Uncontrolled trial, with forced-titration sequential open-label study design. Setting & Participants: 7 boys with genetically confirmed Dent disease and mild phenotype (neither overt sodium wasting nor kidney failure). Intervention: After a 1-month run-in period, patients sequentially received amiloride (5 mg/d) alone (1 month) and then for 3 periods of 2 months in association with increasing doses of HCTZ (< 0.2, 0.2 to 0.4, and 0.4 to 0.8 mg/kg/d). Outcomes: Urinary calcium excretion and extracellular volume indicators. Measurements: At the end of each period, 2 daily 24-hour urinary collections were performed on the days preceding admission. Blood and spot urine samples also were collected. Results: A greater HCTZ dose increased renin, aldosterone, and plasma protein concentrations. Amiloride alone had no effect on calcium excretion. The greatest HCTZ doses decreased spot urinary calcium excretion by 42% compared with baseline (median, 0.3; minimum, maximum, 0.2, 0.8 versus median, 0.8; minimum, maximum, 0.4, 1.1, respectively; P = 0.03). However, patients developed adverse reactions, including muscle cramps (n = 2), biological (n = 7) or symptomatic hypovolemia (n = 1), hypokalemia (n = 4), and hyponatremia (n = 1), which all corrected after treatment withdrawal. Limitation: Small sample size and absence of a control group. Conclusion: HCTZ doses greater than 0.4 mg/kg/d decreased calcium excretion, but were associated with significant adverse events. Thiazide diuretic therapy should be considered with caution in children with Dent disease.