Thiazide Diuretics Arrest the Progression of Nephrocalcinosis in Children With X-Linked Hypophosphatemia

Abstract

ABSTRACT. Objective. X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia, and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with increased urinary calcium excretion and nephrocalcinosis. Thiazide diuretics decrease urinary calcium excretion. The objective of this study was to determine the effect of thiazide diuretics on the clinical and radiologic course of nephrocalcinosis in children with XLH.Methods. The effect of hydrochlorothiazide (HCTZ) on clinical and radiologic progression of nephrocalcinosis was evaluated in 11 children with XLH. All patients had been treated previously with vitamin D and oral phosphate and had radiologic evidence of nephrocalcinosis. The average age of the patients at the start of HCTZ was 6.6 ؎ 1.0 years. The effect of oral HCTZ at 0.8 ؎ 0.1 mg/kg body weight per day given for 3.3 ؎ 0.6 years on the progression of nephrocalcinosis and urinary calcium excretion was evaluated.Results. There was no change in serum phosphorous, calcium, potassium, and chloride after HCTZ therapy. HCTZ therapy increased serum bicarbonate and decreased urinary calcium excretion. The grade of nephrocalcinosis increased from 0.4 ؎ 0.2 to 1.5 ؎ 0.3 in the 2.3 ؎ 0.3 years before initiation of HCTZ therapy, whereas the degree of nephrocalcinosis was stable after 3.3 ؎ 0.6 years of HCTZ therapy (1.5 ؎ 0.3 vs 3.0 ؎ 0.3).Conclusion. HCTZ decreased urinary calcium excretion but did not result in the resolution of nephrocalcinosis. However, when compared with the control period, HCTZ prevented the progression of nephrocalcinosis in children with XLH. Pediatrics 2001;108(1). URL: http:// www.pediatrics.org/cgi/content/full/108/1/e6; X-linked hypophosphatemia, rickets, nephrocalcinosis, thiazide diuretics.ABBREVIATIONS. XLH, X-linked hypophosphatemia; HCTZ, hydrochlorothiazide; TmP/GFR, tubular maximum reabsorption of phosphate per deciliter of glomerular filtration; SEM, standard error of the mean. X -linked hypophosphatemia (XLH) is the most common inherited cause of rickets. It is characterized by hypophosphatemia caused by impaired proximal tubular reabsorption of phosphorous and an inappropriately normal serum level of 1,25(OH) 2 vitamin D. The resulting hypophosphatemia leads to defective bone mineralization. 1 Current therapy includes administration of 1,25(OH) 2 vitamin D (calcitriol) and phosphate to replete urinary phosphate losses without stimulating parathyroid hormone release. 2 Such therapy often leads to hypercalcuria and nephrocalcinosis. 3,4 Nephrocalcinosis can lead to renal tubular acidosis and possibly renal insufficiency. 4 -6 Hypercalcuria also has been shown to be associated with nephrocalcinosis in distal renal tubular acidosis, hyperparathyroidism, prolonged immobilization, Bartter's syndrome, hypophosphatasia, certain tumors, high-dose vitamin D therapy, and idiopathic and drug-induced hypercalcuria. 7-13 Hydrochlorothiazide (HCTZ) decreases urinary calcium excretion. The effect of HCTZ on nephrocalcino...

Resolution of medullary nephrocalcinosis in children with metabolic bone disorders

“…In a small number of children with XLH treated with phosphate and calcitriol, the addition of thiazide/ amiloride presumably provided protection against the development of NC [23]. Seikaly and Baum [24] showed that the addition of thiazides arrested the progression of NC in their XLH patients; however, no resolution of NC was observed (personal communication). We are not aware of any previous study showing ultrasonographic resolution of nephrocalcinosis in patients with XLH spontaneously or after treatment with anticalciuric diuretics.…”

The enigma of hyperparathyroidism in hypophosphatemic rickets

“…However, excessive doses, e.g., more than 50 ng/kg per day of 1,25(OH) 2 D 3 , should not be used long term [53,54]. For treatment of hypercalciuria, thiazides might be considered [55].…”

Types of Rickets, Dental and Histologic Findings: Review of the Literature

“…Commonly, infants younger than six months present with hypocalcemic tetany or seizures, whereas older children present with failure to thrive or skeletal deformiti es 9 . Vitamin D-dependent rickets, type I results from abnormaliti es in the gene coding for 25 10,11 . Hypophosphatemic vitamin D-resistant rickets or X linked hypophosphataemia (XLH) is a hereditary disease manifesti ng marked hypophosphataemia caused by renal tubular loss of phosphate into urine and an associated decrease in the calcium and potassium ion product.…”

“…The systemic fi ndings of XLH include bowed legs because of a body load showing immature skeletal bone calcifi cati on, spinal curvature deformiti es and beading of the ribs called rachiti c rosary [25][26][27] . Other causes of rickets include renal disease, medicati ons, and malabsorpti on syndromes (Table 1 8, [9][10][11][12][13][14][15] ).…”

“…However, impaired lα(OH)2D metabolism has also been suggested 6,7 . Various types of rickets with clinical features and treatments defi ned on Table 1 8, [9][10][11][12][13][14][15] . The aim of this literature review is to present various types of rickets with clinical features and the dental fi ndings, preventi ve measurements and treatments.…”