Is skeletal response to parathyroid hormone abnormal in experimental renal failure?
It is widely believed that skeletal resistance is the mechanism of impaired calcemic response to parathyroid hormone (PTH) in renal failure. The action of PTH not only involves skeletal mobilization of Ca, it may also stimulate intestinal absorption of Ca and renal conservation of Ca. We have examined each of these factors and studied the calcemic response to PTH in renal failure. PTH, 3 U/hr/100 gm, was infused for 5 hours in rats with renal failure 3 weeks after a five-sixths nephrectomy. In nonfasted animals, the post-PTH increments of total plasma Ca (0.71 +/- 0.06 mg/dl) and ionized Ca (0.37 +/- 0.06 mg/dl) of control sham-operated rats were significantly greater than those of rats with renal failure (plasma Ca 0.37 +/- 0.02 mg/dl and plasma ionized Ca 0.17 +/- 0.01 mg/dl both p less than 0.001). Urinary Ca excretion rate remained unchanged during PTH infusion despite the increase in plasma Ca. Plasma levels of calcitriol after PTH injection were higher in control rats (257 +/- 18 pg/ml) than in rats with renal failure (162 +/- 5 pg/ml, p less than 0.001). Pretreatment of rats with renal failure with 50 ng calcitriol intravenously corrected the abnormal calcemic response to PTH. To exclude the PTH effect on intestinal Ca absorption, PTH infusion was carried out in animals fasted for 18 hours. The post-PTH increments of Ca were no longer different between rats with renal failure (plasma Ca 0.37 +/- 0.04 mg/dl, plasma ionized Ca 0.20 +/- 0.01 mg/dl) and control rats (plasma Ca 0.37 +/- 0.03 mg/dl, plasma ionized Ca 0.19 +/- 0.01), suggesting that skeletal mobilization of Ca was similar between the two groups of animals. We conclude that lack of intestinal response to PTH rather than skeletal resistance was the mechanism of impaired calcemic response to PTH in this model of renal failure.
Patel
S
S
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Hsu
C H
CH
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D005215:Fasting; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats
D010281:Parathyroid Hormone; D002117:Calcitriol; D002118:Calcium