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Sodium transport and bone mineral density in hypercalciuria with thiazide treatment
G S Reusz1, M Dobos, B Vásárhelyi
1First Department of Pediatrics, Semmelweis University Medical School, Budapest, Hungary.
Insights
Idiopathic hypercalciuria (IHU) in children is linked to abnormal sodium transport in red blood cells. Chronic thiazide treatment corrects these cellular transport issues and improves bone mineral density.
Area of Science:
- Pediatric Nephrology
- Cellular Physiology
- Endocrinology
Background:
- Idiopathic hypercalciuria (IHU) is a common cause of nephrolithiasis in children.
- Cellular sodium handling, particularly erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport, may be altered in IHU.
- The impact of chronic thiazide therapy on these cellular transport mechanisms and bone mineral density in children with IHU requires further investigation.
Purpose of the Study:
- To evaluate erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport activities in children with IHU.
- To assess the effects of chronic hydrochlorothiazide administration on these cellular transport parameters.
- To determine the influence of chronic thiazide treatment on bone mineral density in children with IHU.
Main Methods:
- Measurement of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport activities in children with IHU and healthy controls.
- Administration of chronic hydrochlorothiazide to patients with IHU.
- Monitoring of urinary calcium excretion, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) Z scores before and during treatment.
Main Results:
- Children with IHU exhibited significantly lower erythrocyte Na+/K+-ATPase activity compared to controls.
- Thiazide treatment significantly reduced urinary calcium excretion and slightly suppressed iPTH levels.
- Following thiazide administration, erythrocyte Na+/K+-ATPase activity increased, Na+/Li+ countertransport decreased, and bone mineral density Z scores improved.
Conclusions:
- IHU is associated with erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport abnormalities.
- Chronic hydrochlorothiazide administration effectively corrects these cellular transport defects in children with IHU.
- Thiazide treatment demonstrates a positive impact on bone mineral density in children with IHU, potentially by influencing renal tubular transport mechanisms.
Abstract:
Erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6-16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean +/- SEM 2,156 +/- 110 micromol P/l erythrocyte per hour vs. 3,165 +/- 175, P < 0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90 +/- 0.07 mmol/mmol versus 0.51 +/- 0.06 respectively, P < 0.01. The corresponding iPTH levels were 5.9 +/- 0.6 pmol/l and 5.1 +/- 0.7, P < 0.05. The Na+/K+-ATPase activity increased significantly (2,769 +/- 169 micromol P/l erythrocyte per hour vs. 2,156 +/- 110 in the control period, P < 0.01) and the Na+/Li+ countertransport decreased (268 +/- 28 micromol Li/l erythrocyte per hour vs. 328+26 in the control period, P < 0.03). The bone mineral density Z score rose from -1.3 +/- 0.26 to -0.8 +/- 0.22 (P < 0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.