Idiopathic infantile hypercalcemia: case report and review of the literature

The widespread use of supplemental vitamin D has dramatically reduced the incidence of rickets. While generally considered a safe practice, there is potential for toxicity in patients with idiopathic infantile hypercalcemia (IIH). Inadequate 24-hydroxylase-enzyme activity renders these individuals unable to degrade active vitamin D, resulting in hypercalcemia due to increased intestinal calcium absorption, decreased renal calcium excretion, and increased osteoclastic bone activity. Clinicians should be aware that even therapeutic doses of vitamin D can prove harmful for patients with

Effects of furosemide on renal calcium handling

Furosemide is a loop diuretic agent that has been used to treat hypercalcemia because it increases renal calcium excretion. The effect of furosemide on calcium transport molecules in distal tubules has yet to be investigated. We conducted studies to examine the effects of furosemide on renal calcium excretion and expression of calcium transport molecules in mice. Mice were administered with a single dose of furosemide (15 mg/kg) and examined 4 h later or were given twice-daily furosemide injections for 3 days. To evaluate the effects of volume depletion, drinking water was supplemented with salt. Our results showed that, in acute experiments, furosemide enhanced urinary calcium excretion, which was associated with a significant increase in mRNA levels of TRPV5, TRPV6, and calbindin-D28k but not calbindin-D9k as measured by real-time PCR (TRPV5 and TRPV6 are transient receptor potential vanilloid 5 and 6). Chronic furosemide administration induced three- to fourfold increases in urinary calcium excretion and elevated mRNA levels of TRPV5, TRPV6, calbindin-D28k, and calbindin-D9k without or with salt supplement. Similar upregulation of calcium transport molecules was observed in mice with gentamicin-induced hypercalciuria. Coadministration of chlorothiazide decreased furosemide-induced calciuria, either acutely or chronically, although still accompanied by upregulation of these transport molecules. Immunofluorescent staining studies revealed comparably increased protein abundance in TRPV5 and calbindin-D28k. We conclude that furosemide treatment enhances urinary calcium excretion. Increased abundance of calcium transport molecules in the distal convoluted tubule represents a solute load-dependent effect in response to increased calcium delivery and serves as a compensatory adaptation in the downstream segment.

Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women

High postmenopausal endogenous estrogen concentrations are an important determinant of preservation of bone mass and reduced fracture in elderly women. Calcium supplementation can also reduce bone loss in these patients, suggesting an interaction between estrogen deficiency and calcium balance. Potential mechanisms of estrogen on calcium transport include direct effects on the bone, the kidney, and the bowel. Previous studies have demonstrated effects of estrogen on renal phosphate handling. We have used a cross-sectional, population-based analysis of biochemical data obtained from ambulant elderly women to determine the association of endogenous estradiol with urine calcium and phosphorus excretion. The subjects were 293 postmenopausal women >70 yr old. Factors associated with renal calcium and phosphate excretion were measured, including the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol, and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE) was calculated from a previously described formula. A high plasma estradiol concentration ( r2 = 0.023, P = 0.01) and a high FE ( r2 = 0.045, P = 0.001) were associated with reduced renal calcium excretion. The estradiol and FE effect on renal calcium excretion remained significant after adjusting for calcium filtered at the glomerulus and serum PTH. A high FE was associated with a reduced renal phosphate threshold in univariate analysis ( r2 = 0.023, P = 0.010). The effect remained significant after adjustment for serum PTH. The size of the effect of the FE was of the same order of magnitude as the effect of PTH on reducing renal calcium excretion and increasing renal phosphate excretion. These data support in vitro and animal data demonstrating an effect of estradiol on renal calcium and phosphate handling and indicate that, in elderly postmenopausal women, the effect is of a similar magnitude to the well-recognized effects of PTH on these physiologically regulated parameters.