In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3

Background. Although it effectively suppresses parathyroid hormone (PTH) secretion, vitamin D [1,25(OH)(2)D-3] therapy often causes tissue calcification over the long term. In patients on chronic dialysis, cardiovascular calcification is clearly linked to an unfavourable prognosis. In pre-dialysis patients, renal calcification of the kidney leads to the deterioration of renal function. Methods. We compared the propensities of 22-oxacalcitriol (OCT), with lesser calcaemic action, and 1,25(OH)(2)D-3 for producing their potential side effects in rats: (i) metastatic calcification of heart and aorta, and (ii) renal dysfunction with nephrocalcinosis, using the same effective doses for hyperparathyroidism. OCT (1.25 and 6.25 mug/kg) or 1,25(OH)(2)D-3 (0.125 and 0.625 mug/kg) solutions were administered intravenously to subtotally nephrectomized (SNX) rats three times weekly for 2 weeks. Results. Despite the suppression of PTH to comparable levels, the calcification of the hearts, aortas and kidneys in the 1,25(OH)(2)D-3-treated group was significantly greater than in the OCT-treated group. Of interest was that, in the OCT (6.25 mug/kg) group, the degree of calcification in hearts, aortas and kidneys were distinctly lower than those in the 1,25(OH)(2)D-3 (0.125 mug/kg) group despite the comparable serum Ca x Pi products. Therefore, there may be different mechanisms behind the calcifications resulting from OCT and 1,25(OH)(2)D-3. Deterioration of renal function, tubular changes, and atypical hyperplasia of proximal tubules associated with calcification were more severe in the 1,25(OH)(2)D-3-treated group than in the OCT-treated group. Conclusions. These results indicate that OCT may be an effective agent for the suppression of PTH with a lesser risk of cardiovascular calcification or deterioration of residual renal function.