Hypercalciuria is the major risk factor promoting stone formation in
Dent's disease, also known as X-linked recessive
nephrolithiasis, but the effects of
diuretics on
calcium excretion and other stone risk factors in this disease are unknown. This study examined urine composition in eight male patients with
Dent's disease, ages 6 to 49 yr, all of whom were hypercalciuric and had inactivating mutations of CLCN5. Eight males, ages 7 to 34 yr, with idiopathic
hypercalciuria (IH) served as controls. Patients were instructed to maintain a consistent intake of
sodium,
potassium,
calcium, and
protein. Two consecutive 24-h urine collections were obtained after a baseline period and after 2 wk of
chlorthalidone (25 mg),
amiloride (5 mg), and the two
diuretics in combination, with a week off
drug separating the treatment periods in a randomized crossover design. Doses were reduced by half in boys under age 12 yr.
Chlorthalidone alone (P < 0.002) and the combination of
chlorthalidone and
amiloride (P < 0.003) reduced
calcium excretion significantly in either patient group. With
chlorthalidone,
calcium excretion fell to normal (<4.0 mg/kg per d) in all but one patient in each group.
Amiloride alone had no significant effect on urinary
calcium excretion, in either patient group. In patients with
Dent's disease during
chlorthalidone therapy, the supersaturation ratios for
calcium oxalate and
calcium phosphate fell by 25% and 35%, respectively. Mean
citrate excretion was reduced by
chlorthalidone (P <.04) and by
chlorthalidone in combination with
amiloride (P <.02). There were no significant differences in the responses to these
diuretics between the patient groups in any of the urinary parameters. The intact hypocalciuric response to a
thiazide diuretic indicates that inactivation of the
ClC-5 chloride channel does not impair
calcium transport in the distal convoluted tubule and indicates that
thiazides should be useful in reducing the risk of
kidney stone recurrence in patients with
Dent's disease.