Effect of thiazides on the hypercalciuria of phosphate depletion.

The present investigation was carried out to examine the effect of thiazides on the hypercalciuria of phosphate depletion. Studies were done on 160 to 190 gm male rats, utilizing metabolic balance techniques. Animals were assigned to a phosphate-deficient diet and divided into a vehicle and thiazide-treated group. Both groups raised on a phosphate-deficient diet developed hypophosphatemia, hypercalciuria, and hypercalcemia; the latter was significantly greater in the thiazide-treated group. The magnitude of the hypercalciuria was significantly smaller in the thiazide-treated group. This occurred despite a significantly greater elevation in the concentration of serum calcium and its filtered load in the rats treated with the diuretic. Thiazides failed to produce natriuresis in the phosphate-deficient rats, suggesting a possible tubular resistance to the natriuretic action of the drug in phosphate depletion. Our data demonstrate that thiazide administration blunts the hypercalciuria of phosphate depletion. The results are consistent with the postulates that (1) phosphate depletion suppresses tubular calcium reabsorption at a site proximal to the segment where thiazides enhance calcium transport or (2) thiazide enhances calcium reabsorption at a terminal site in the nephron where a decrease in calcium transport may occur during phosphate depletion.