The Influence of 24,25(OH) 2 D 3 on the Calcemic Effect of 1,25(OH) 2 D in Rats with Chronic Renal Failure Is Parathyroid Hormone Dependent

Abstract

Previous studies from our laboratory have shown that 24,25(OH)₂D₃ attenuates the calcemic effect of 1,25(OH)₂ D ₃ in rats with reduced renal mass. This study was undertaken to clarify the role of parathyroid hormone in this response. Adult rats (n = 27) with reduced renal mass after parathyroidectomy with an initial plasma calcium of 3.7 ± 0.1 mEq/liter were divided into four groups: (i) control rats and rats treated with (ii) 24,25(OH)₂D₃, (iii) 1,25(OH)₂D₃, and (iv) both 1,25 and 24,25(OH)₂D₃. After 4 days significant hypercalcemia was seen in PTX animals receiving 1,25(OH)₂D₃ alone or in combination with 24,25(OH)₂D₃. Plasma calcium in the combined therapy rats (7.42 ± 0.22 mEq/liter) was significantly higher than in those treated with 1,25(OH)₂D₃ alone (6.68 ± 0.22 mEq/liter, P < 0.05). After 8 days, plasma calcium was higher in the rats treated with 1,25(OH)₂D₃ but was of same magnitude in those treated with 1,25(OH)₂D₃ alone or in combination with 24,25(OH)₂D₃. In contrast, in a subset of rats (n = 35) with reduced renal mass but intact parathyroid glands similarly treated with the vitamin D metabolites, a blunted calcemic response was seen after the combination of 1,25(OH)₂D₃ with 25,25(OH)₂D₃ administration alone.

These results show that in rats with reduced renal mass, 24,25(OH)₂D₃ attenuates the calcemic effect of 1,25(OH)₂D₃ only in the presence of intact parathyroid glands. The different calcemic responses to 1,25 or combined 1,25 and 24,25(OH)₂D₃ in intact or parathyroidectomized rats with chronic renal insufficiency may result from different interaction between the vitamin D metabolites and the parathyroid hormone, presumably at the level of bone.