Responsiveness of Hypercalciuria to Thiazide in Dent’s... : Journal of the American Society of Nephrology (original) (raw)

Mineral Metabolism and Bone Disease

Raja, Khalid A*; Schurman, Scott†; D’Mello, Richard G.*; Blowey, Douglas§; Goodyer, Paul¶; Van Why, Scott†; Ploutz-Snyder, Robert J.*; Asplin, John#; Scheinman, Steven J.*

Departments of *Medicine and †Pediatrics, SUNY Upstate Medical University, Syracuse, New York; §Section of Pediatric Nephrology, The Children’s Mercy Hospital, Kansas City, Missouri; ¶Department of Pedatrics, McGill University, Montreal, Canada; ‡Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut; and #Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois.

Correspondence to Dr. Steven J. Scheinman, Professor of Medicine, SUNY Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210. Phone 315-464-5290; Fax: 315-464-5295;E-mail: [email protected]

Accepted July 29, 2002

Received September 17, 2001

Abstract

ABSTRACT. 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.