Calcemic response to parathyroid hormone in renal failure: Role of calcitriol and the effect of parathyroidectomy

摘要

Calcemic response to parathyroid hormone in renal failure: Role of calcitriol and the effect of parathyroidectomy. Hyperparathyroidism due to renal failure begins in the early stages of renal insufficiency and is in part secondary to skeletal resistance to the calcemic action of parathyroid hormone (PTH). Factors which have been reported to reduce the calcemic response to PTH include: decreased calcitriol levels, hyperphosphatemia and down regulation of PTH receptors in bone. While hyperphosphatemia may directly decrease the calcemic response to PTH, it may also act indirectly by a suppression of calcitriol synthesis. In this study, the effect of calcitriol on the calcemic response to PTH was evaluated in normal rats and in rats with moderate and advanced renal failure. To determine the combined effect of calcitriol and phosphorus on the calcemic response to PTH, rats receiving calcitriol were fed either a high (1.0%) or low (0.2%) phosphorus diet during a 48-hour PTH infusion. In advanced renal failure, calcitriol administration increased the calcemic response to PTH independent of the dietary phosphorus intake. During ingestion of a low phosphorus diet, a 48 hour PTH infusion resulted in a serum calcium level of 13.7 0.5 and 12.1 0.2 mg/dl(P < 0.02) with and without calcitriol administration, respectively. In normal rats and in rats with moderate renal failure, calcitriol administration improved the calcemic response only during a high phosphorus intake. After a 48-hour PTH infusion in normal rats, the serum calcium levels with and without calcitriol were 16.1 0.9 and 14.8 0.6 mg/dl, P < 0.01 respectively; in rats with moderate renal failure, calcitriol administration increased serum calcium, 13.2 0.5 versus 11.2 0.4 mg/dl, P < 0.01. Since calcitriol administration and a low phosphorus diet improved but did not normalize the calcemic response to PTH, a selective parathyroidectomy was performed to eliminate the effect of down regulation of bone receptors for PTH induced by high PTH levels. Whereas calcitriol increased the calcemic response by only 31%, parathyroidectomy corrected the calcemic response to PTH even in the presence of renal failure. In conclusion, the effect of calcitriol administration on the calcemic response to PTH is modified by the magnitude of phosphate retention and the degree of renal failure. Finally, the finding that parathyroidectomy normalized the calcemic response to PTH in azotemic rats suggests that a high PTH level is an essential factor in the impaired calcemic response to PTH in renal failure.