RELATIVE EFFECTS OF PTH AND DIETARY PHOSPHORUS ON CALCITRIOL PRODUCTION IN NORMAL AND AZOTEMIC RATS

In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosp horus retention. Our goal was to evaluate the relative effect that hig h PTH levels and increased dietary phosphorus had on calcitriol produc tion in normal rats (N) and rats with moderate renal failure (Nx). Nor mal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) ra ts with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of ra t 1-34 PTH, 0.022 mu g/hr/100 g body wt, using a miniosmotic Alzet pum p. To test the effect of dietary phosphorus, rats received either a mo derate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days . The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allow ed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MP D groups respectively, P < 0.05). Even in N rats on a HPD, high PTH le vels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintai n normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IP TG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg /ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were lo w in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were depr ived of the adaptative increase in endogenous PTH production. In concl usion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention.