24,25(OH) 2 D 3 Attenuates the Calcemic Effect of 1,25(OH) 2 D 3 in Rats with Reduced Renal Mass

Abstract

The present study was undertaken to evaluate the effect of 24,25(OH)₂D₃ on serum calcium concentration in rats with reduced renal mass. Adult 5/6 nephrectomized male rats were divided into four groups: (i) control rats, (ii) rats treated with 1,25(OH)₂D₃, (iii) rats treated with 24,25(OH)₂D₃, and (iv) rats treated with 1,25(OH)₂D₃ and 24,25(OH)₂D₃. After 4 days, serum calcium in the 1,25(OH)₂D₃-treated group was 7.13 ± 0.32 meq/liter (P < 0.001 vs control). With the combination of 1,25(OH)₂D₃ and 24,25(OH)₂D₃ serum calcium was higher than that in control, 6.25 ± 0.5 meq/liter (P < 0.001 vs control), but lower than that in rats receiving 1,25(OH)₂D₃ alone (P < 0.05). No change in serum calcium was seen in animals treated with 24,25(OH)₂D₃ alone. On the eighth day serum calcium in the 1,25(OH)₂D₃-treated group, 6.52 ± 0.25, was higher than in the 1,25(OH)₂D₃ + 24,25(OH)₂D₃ group, 5.87 ±0.17 meq/liter, P < 0.05, P < 0.001 vs control. In both 1,25(OH)₂D₃- and 1,25(OH)₂D₃ + 24,25(OH)₂D₃-treated rats, hypercalciuria of similar magnitude occurred on the fourth and eighth day of treatment. No change in urinary calcium was seen in the control and 24,25(OH)₂D₃-treated rats. Thus, in 5/6 nephrectomized rats combined administration of 1,25(OH)₂D₃ and 24,25(OH)₂D₃ attenuates the calcemic response to 1,25(OH)₂D₃ without changes in urinary calcium excretion. These observations suggest that the effect of 24,25(OH)₂D₃ on serum calcium is different in 5/6 nephrectomized rats as compared to normal rats, in which an augmentation of serum calcium was observed following administration of both vitamin D metabolites. The effect of 24,25(OH)₂D₃ on serum calcium in rats with reduced renal mass may result from a direct effect of 24,25(OH)₂D₃ on the bone.