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

Abstract

Background. Although it effectively suppresses parathyroid hormone (PTH) secretion, vitamin D [1,25(OH)₂D₃] 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)₂D₃ 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 μg/kg) or 1,25(OH)₂D₃ (0.125 and 0.625 μg/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)₂D₃-treated group was significantly greater than in the OCT-treated group. Of interest was that, in the OCT (6.25 μg/kg) group, the degree of calcification in hearts, aortas and kidneys were distinctly lower than those in the 1,25(OH)₂D₃ (0.125 μg/kg) group despite the comparable serum Ca × Pi products. Therefore, there may be different mechanisms behind the calcifications resulting from OCT and 1,25(OH)₂D₃. Deterioration of renal function, tubular changes, and atypical hyperplasia of proximal tubules associated with calcification were more severe in the 1,25(OH)₂D₃-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.