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 ofsecondary hyperparathyroidism. Since parathyroidectomy normalizesthe calcaemic response to PTH in uraemic animals, the increasein PTH levels has been advanced as a cause of skeletal resistanceto the calcaemic action of PTH. This study was designed to evaluatein uraemic rats the effect of normal PTH levels on the calcaemicresponse to PTH. METHODS: To maintain normal PTH levels, rats were parathyroidectomized(PTX) and rat 1–34 PTH was infused at a rate of 0.022µg/100 g per hour via a subcutaneously implanted miniosmoticpump; this rate of infusion was considered to be the normalPTH replacement dose since it normalized serum calcium and phosphorusin PTX rats with normal renal function. Two separate studieswere performed. In the first study, rats were maintained ona moderate-phosphorus (0.6%) diet and rats were divided intofour groups: (I) normal; (II) uraemic; (III) PTX with normalPTH 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 hyperparathyroidismin rats with intact parathyroid glands; an additional group(V) identical to group IV except that rats received daily calcitriolwas included. After 14 days, rats received a 48-h infusion ofhigh-dose rat 1–34 PTH (0.11 µg/100 g per hour)to evaluate the calcaemic response to PTH. RESULTS: The calcaemic response to PTH was similar in normal rats andPTX rats with PTH replacement on both a moderate and high-phosphorusdiet. In uraemic rats, the calcaemic response to PTH was decreasedand the maintenance of normal PTH levels by PTH replacementdid not correct the decreased calcaemic response to PTH; moreover,calcitriol supplementation did not improve the calcaemic responseto PTH. Finally, hypocalcaemia was observed in uraemic ratswith PTH replacement and was more profound than in rats on ahigh-phosphorus diet. CONCLUSIONS: This study demonstrates that the maintenance of a normal PTHlevel in uraemic rats did not correct the impaired calcaemicresponse to PTH, suggesting that factors intrinsic to uraemia,independent of phosphorus, calcitriol, and PTH participate inthe decreased calcaemic response to PTH in uraemia.