The potential role of salt abuse on the risk for kidney stone formation.

The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease.

Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free 1,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P less than 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 +/- 14 micrograms/ml and 371 +/- 46 micrograms/ml, respectively) than normal subjects (436 +/- 33 micrograms/ml) and had significantly higher percent free 1,25(OH)2D (0.98 +/- 0.13% and 1.27 +/- 0.14%, respectively) compared to 0.63 +/- 0.03% (P less than 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status.

Fluoride rapidly and transiently raises intracellular calcium in human osteoblasts.

We examined the effect of fluoride (F) on intracellular ionic calcium [Ca2+]i in normal human osteoblasts maintained in culture. Cells were grown on glass coverslips to near-confluency and loaded with the Ca-sensitive dye, fura-2AM. Fluorescence changes were monitored in single cells using an inverted microscope coupled by fiberoptic to a microspectrofluorometer. The addition of F (100 ng/mL) to the medium promoted a rapid and significant increase in free [Ca2+]i from a resting level of 245 +/- 36 SE nM to a peak concentration of 440 +/- 51 nM (p less than 0.04). This increase in [Ca2+]i began at 10-20 s after addition of F and was maximal by 30 s. Intracellular [Ca2+]i levels then returned to near resting values by 60-80 s after F addition. This response was evident with as little as 25 ng/ml of fluoride and was dose dependent up to 500 ng/ml. At concentrations greater than 500 ng/ml, there appeared to be an attenuation of the rise in [Ca2+]i. The observed rise in [Ca2+]i was dependent on extracellular calcium since lowering extracellular calcium concentration or incubation with calcium channel blockers abolished the response. This observation supports a role of increased [Ca2+]i as one of the initial events of fluoride on action osteoblasts.