To clarify the role of vitamin D in renal phosphate transport, weanling rats were fed a vitamin D-deficient diet containing 1.8% calcium and 1.2% phosphorus. After 5-6 wk, the rats were normocalcemic, normophosphatemic, and had normal levels of PTH. Assays of vitamin D metabolites revealed undetectable plasma levels of 25(OH)D, and 1,25(OH)2D levels of 92 ± 16 pg/ml in partially vitamin D-depleted (PVDD) rats and 169 ± 58 pg/ml in normal rats. PVDD rats had increased phosphate excretion, both absolute and fractional, and a decrease in Na+ gradient-dependent P(i) transport in proximal tubular brush border membrane vesicles (BBMV) prepared from their kidneys. Vitamin D repletion of PVDD rats with 1,25(OH)2D3, 15 pmol/100 g body wt, decreased fractional excretion of P(i) from 22.6 ± 1.9 to 13.5 ± 1.3%; the latter values were similar to normal rats. Repletion with 1,25(OH)2D3 also increased Na+-dependent phosphate transport in BBMV from 322 ± 24 pmol·mg protein-1·15 s-1 in BBMV from PVDD rats to 698 ± 70 pmol·mg protein-1·15 s-1. Repletion with larger doses of 1,25(OH)2D3 produced hypercalcemia and hyperphosphatemia from intestinal absorption, an increase in phosphate excretion, and a blunted response of P(i) transport to 1,25(OH)2D3. Prevention of hyperphosphatemia by dietary adjustments allowed full expression of the stimulatory effects of 1,25(OH)2D3 on P(i) transport. These latter data may partially explain the inhibitory effects reported in prior studies in which plasma P(i) was not controlled and the larger doses of 1,25(OH)2D3 administered. The studies reported here clearly demonstrate that vitamin D depletion is associated with decreased P(i) transport by the kidney that is rapidly corrected by physiologic amounts of 1,25(OH)2D3. The stimulatory effect of 1,25(OH)2D3 on P(i) transport is manifest in the brush border membrane of renal proximal tubular cells at the level of the Na+-dependent active transport mechanism.
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Jan 1 1984|