Abnormal calcaemic response to PTH in the uraemic rat without secondary hyperparathyroidism

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 levels has been advanced as a cause of skeletal resistance to the calcaemic action of PTH. This study was designed to evaluate in uraemic rats the effect of normal PTH levels on the calcaemic response to PTH. METHODS: To maintain normal PTH levels, rats were parathyroidectomized (PTX) and rat 1-34 PTH was infused at a rate of 0.022 microg/100 g per hour via a subcutaneously implanted miniosmotic pump; this rate of infusion was considered to be the normal PTH replacement dose since it normalized serum calcium and phosphorus in PTX rats with normal renal function. 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-phosphorus (1.2%) diet was given to increase the magnitude of hyperparathyroidism in rats with intact parathyroid glands; an additional group (V) identical to group IV except that rats received daily calcitriol was included. After 14 days, rats received a 48-h infusion of high-dose rat 1-34 PTH (0.11 microg/100 g per hour) to evaluate the calcaemic response to PTH. Results. The calcaemic response to PTH was similar in normal rats and PTX rats replacement on both a moderate and high-phosphorus diet. In uraemic rats, the calcaemic response to PTH was decreased 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. Finally, 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 in uraemic rats did not correct the impaired calcaemic response to PTH, suggesting that factors intrinsic to uraemia, independent of phosphorus, calcitriol, and PTH participate in the decreased calcaemic response to PTH in uraemia.