The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure

Abstract

Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (< 0.05%). With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P < 0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05). Dietary calcium loading either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.