The Importance of Phosphate in Regulating Plasma 1,25-(OH)₂-Vitamin D Levels in Humans: Studies in Healthy Subjects, in Calcium-Stone Formers and in Patients with Primary Hyperparathyroidism*

We observed that plasma 1,25-(OH)2-D concentrations average 87 ± 30 SD pmol/1 in 48 healthy adults without a personal or family history of kidney stones. Plasma 1,25-(OH)2-D concentrations were significantly elevated among 26 patients with recurrent calcium-containing renal stones and hypophosphatemia: 150 ± 74 pmol/1; P < 0.001, andamong 9 patients with provenparathyroid adenoma and hypophosphatemia: 200 ± 54 pmol/1; P< 0.001. Plasma 1,25-(OH)2-D levels in these 3 groups were inversely correlated with serum phosphate concentration: plasma1,25-(OH)2-D, pmol/1 = 282 – 141 × serumPO4, mmol/1; r = 0.51; P < 0.001. During dietary PO4 deprivation lasting 11 to 16 days in 10 healthy women, serum PO4 fell and plasma 1,25-(OH)2-D concentrations rose whereas in 8 healthy menneither serum PO4 nor 1,25-(OH)2-D concentrations changed. The change from control in plasma 1,25-(OH)2-D levels were correlated with the change from control in serum PO4 concentrations: Δ1,25-(OH)2-D, pmol/1 = 1 - 82 × Δserum PO4 mmol/1; r = 0.59; P < 0.01. We conclude that reductions in serum PO4 concentrations, either directly orindirectly, stimulate renal synthesis of 1,25-(OH)2-D in humans.