CALCEMIC RESPONSE TO PARATHYROID-HORMONE IN RENAL-FAILURE - ROLE OF PHOSPHORUS AND ITS EFFECT ON CALCITRIOL

The calcemic response to parathyroid hormone (PTH) is decreased in renal failure. The reduction of hyperphosphatemia improves the calcemic response to PTH in animals with advanced renal failure. However, since low calcitriol levels in renal failure may also contribute to the decreased calcemic response to PTH, the improved calcemic response observed during the reduction of serum phosphorus may be partially mediated by an increase in serum calcitriol levels. The present study evaluated the calcemic response to PTH in rats with moderate and advanced renal failure and how this response was modified by a high and a low phosphorus diet. In addition, the effect of a change in dietary phosphorus on calcitriol levels was also evaluated. A 48-hour continuous infusion of 1-34 rat PTH increased the serum calcium level to 18.2 +/- 0.4 mg/dl in normal rats, versus 13.7 +/-9 and 12.1 +/- 0.2 mg/dl in rats with moderate and advanced renal failure, respectively. During the PTH infusion, a high phosphorus diet increased the serum phosphorus and resulted in a reduced calcemic response to PTH at each level of renal function; respective serum calcium levels were 13.8 +/- 0.6 mg/dl in normals, 11.2 +/- 0.2 mg/dl in moderate renal failure and 9.6 +/- 0.5 mg/dl in advanced renal failure. In normal rats and in rats with moderate renal failure, dietary phosphorus restriction during the PTH infusion increased serum calcitriol levels. In rats with advanced renal failure, serum calcitriol levels were lower than in the other two groups and were not affected by changes in dietary phosphorus. In an additional group of rats, parathyroidectomy corrected the calcemic response to PTH, suggesting that resistance to the calcemic action of PTH in renal failure requires the presence of circulating levels of PTH. In conclusion. a decreased calcemic response to PTH was present not only in advanced renal failure but also in moderate renal failure. This abnormal response to PTH appears to be multifactorial. Phosphorus restriction improved the calcemic response to PTH and this effect could have been in part due to higher values of calcitriol; however, in advanced renal failure, calcitriol levels were not influenced by dietary phosphorus, and thus, the increased calcemic response to PTH induced by phosphorus restriction was independent of calcitriol. Finally, down regulation of bone receptors for PTH appears to play a major role in the decreased calcemic response to PTH in renal failure.