Hyperphosphatemia modestly retards parathyroid hormone suppression during calcitriol-induced hypercalcemia in normal and azotemic rats

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.