ABNORMAL CALCEMIC RESPONSE TO PTH IN THE UREMIC RAT WITHOUT SECONDARYHYPERPARATHYROIDISM

Background. Skeletal resistance to the calcaemic action of parathyroid hormone (PTH) is an important pathogenic factor in the development of secondary hyperparathyroidism. Since parathyroidectomy normalizes the calcaemic response to PTH in uraemic animals, the increase in PTH lev els has been advanced as a cause of skeletal resistance to the calcaem ic action of PTH. This study was designed to evaluate in uraemic rats the effect of normal PTH levels on the calcaemic response to PTH. Meth ods. To maintain normal PTH levels, rats were parathyroidectomized (PT X) and rat 1-34 PTH was infused at a rate of 0.022 mu g/100 g per hour via a subcutaneously implanted miniosmotic pump; this rate of infusio n was considered to be the normal PTH replacement dose since it normal ized serum calcium and phosphorus in PTX rats with normal renal functi on. Two separate studies were performed. In the first study, rats were maintained on a moderate-phosphorus (0.6%) diet and rats were divided into four groups: (I) normal; (II) uraemic; (III) PTX with normal PTH replacement; and (IV) uraemic with PTX and normal PTH replacement. In a second study, the groups were the same except that a high-phosphoru s (1.2%) diet was given to increase the magnitude of hyperparathyroidi sm in rats with intact parathyroid glands; an additional group (V) ide ntical to group IV except that rats received daily calcitriol was incl uded. After 14 days, rats received a 48-h infusion of high-dose rat 1- 34 PTH (0.11 mu g/100 g per hour) to evaluate the calcaemic response t o PTH. Results. The calcaemic response to PTH was similar in normal ra ts and PTX rats with PTH replacement on both a moderate and high-phosp horus diet. In uraemic rats, the calcaemic response to PTH was decreas ed and the maintenance of normal PTH levels by PTH replacement did not correct the decreased calcaemic response to PTH; moreover, calcitriol supplementation did not improve the calcaemic response to PTH. Finall y, hypocalcaemia was observed in uraemic rats with PTH replacement and was more profound than in rats on a high-phosphorus diet. Conclusions . This study demonstrates that the maintenance of a normal PTH level i n uraemic rats did not correct the impaired calcaemic response to PTH, suggesting that factors intrinsic to uraemia, independent of phosphor us, calcitriol, and PTH participate in the decreased calcaemic respons e to PTH in uraemia.