THE INTERACTION OF PTH AND DIETARY PHOSPHORUS AND CALCIUM ON SERUM CALCITRIOL LEVELS IN THE RAT WITH EXPERIMENTAL RENAL-FAILURE

Background. Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phos phorus accumulation and high parathyroid hormone (PTH) levels, both in herent to renal failure, have different effects on calcitriol producti on; moreover, dietary calcium loading may have a separate inhibitory e ffect on calcitriol production. This study was designed to evaluate th e relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. Methods. Renal failure was surgically induced and r ats were divided into normal, moderate renal failure, and advanced ren al failure based on the serum creatinine. Each group was subdivided an d received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or hig h-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 c alcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with eith er a low (0.16%) or high (1%) phosphorus diet; both diets had negligib le calcium (<0.05%). Results. With decreasing renal function, PTH incr eased and was greater in rats fed the HPD than the HCaD; serum calcitr iol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P<0.01). The calcitr iol 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). Conclusions. 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 le vels depend on a complex interaction between PTH and dietary calcium a nd phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.