Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial.

BACKGROUND: Thiazide doses equivalent to 1 to 2 mg/kg/d of hydrochlorothiazide (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.

Hypercalciuric rickets: a rare cause of nephrolithiasis.

An unusual case of rickets associated with hypercalciuria is described. In addition to proteinuria, the patient had phosphaturia, aminoaciduria, renal glucosuria and impaired renal concentration but no renal tubular acidosis. Studies did not support the diagnosis of primary hyperparathyroidism. The findings in the patient were very similar to those in 4 previously reported cases and are suggestive of a new combination of multiple renal tubular defects.

Response to crystalline 1alpha-hydroxyvitamin D3 in vitamin D dependency.

The therapeutic response to chemically synthesized 1alpha-hydroxycholecalciferol (1alpha-OH-D3) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD). The daily maintenance dose for vitamin D2, to prevent signs of vitamin D deficiency in these patients, was 40-54.4 mug/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2 resulted in the ultimate reappearance of the vitamin D depletion syndrome in patients 1 and 2 (Figs. 1 and 2). The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD. Treatment with 1alpha-OH-D3 by mouth in all three patients at dose levels of 1-3 mug/24 hr (80-100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1, 2, and 4). Rickets healed in 7-9 weeks on 1alpha-OH-D3 alone (Fig. 3). The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of 1alpha-OH-D3 was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal. Because the synthesis of 1alpha-OH-D3 is simpler than for 1alpha,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1alpha-OH-D3 to be the agent of choice for treatment of this and analogous diseases.