Effects of 1,25-dihydroxycholecalciferol on phosphate transport in vitamin D-deprived rats

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.