Effect of inorganic phosphate on serum ionized calcium concentration in vitro: a reassessment of the "trade-off hypothesis".

The development of secondary hyperparathyroidism in uremia is thought to be due, in part, to the retention of inorganic phosphate which, as proposed by the "trade-off hypothesis", lowers serum ionized calcium by means of CaHPO4 complex formation. To study this hypothesis, free from hormonal or physiological influence, the effect of changes in inorganic phosphate concentration on calcium ion concentration was examined in vitro in serum and protein-free aqueous solutions. The findings of this study demonstrate that the mean change in ionized calcium in aqueous solution is -0.019 +/- 0.001 mM per 1 mM change in inorganic phosphate, and is not significantly different in serum where the mean change in ionized calcium is -0.018 +/- 0.003 mM per 1 mM change in inorganic phosphate. The results in both aqueous solutions and sera agree closely with values predicted from the K'CaHPO4. Based on these results, the serum inorganic phosphate would have to increase by 1.2 mM (3.7 mg%) before the serum ionized calcium would fall sufficiently (0.025 mM) to stimulate the parathyroid glands. These results indicate that an increase in serum inorganic phosphate to as great as 1 mM/liter does not produce a fall in serum ionized calcium by means of direct physicochemical CaHPO4 complex formation great enough to account for the development of secondary hyperparathyroidism.