Hyperphosphatemia Modestly Retards Parathyroid Hormone Suppression during Calcitriol-Induced Hypercalcemia in Normal and Azotemic Rats

Abstract

Background/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. Methods: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1 – normal renal function (NRF) + 0.6% P + vehicle; group 2 – NRF + 0.6% P + CTR; group 3 – renal failure (RF) + 0.6% P + vehicle; group 4 – RF + 1.2% P + CTR; and group 5 – RF + 0.6% P + CTR. Results: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 ± 0.26 and 15.12 ± 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = –0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). Conclusions: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small.

Pretreatment plasma intact parathyroid hormone and serum calcium levels, but not serum phosphate levels, predict the response to maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism

“…21 On the other hand, a recent in vivo study revealed that such an effect of phosphate was rather small. 22 In the present study, the effect of maxacalcitol therapy was not predictable by pretreatment Pi levels. Because the pretreatment Pi levels may not have represented the Pi levels throughout the observation period, we do not insist, from this result, that serum Pi levels have no effect on parathyroid function.…”