Patel S, Hsu C H
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
J Lab Clin Med. 1988 Sep;112(3):387-93.
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.
人们普遍认为，骨骼抵抗是肾衰竭时对甲状旁腺激素（PTH）的钙调节反应受损的机制。PTH的作用不仅涉及骨骼对钙的动员，还可能刺激肠道对钙的吸收以及肾脏对钙的保留。我们研究了这些因素中的每一个，并研究了肾衰竭时对PTH的钙调节反应。在六分之五肾切除术后3周的肾衰竭大鼠中，以3 U/小时/100克的速度输注PTH 5小时。在非禁食动物中，假手术对照大鼠在输注PTH后总血浆钙（0.71±0.06毫克/分升）和离子钙（0.37±0.06毫克/分升）的增加显著大于肾衰竭大鼠（血浆钙0.37±0.02毫克/分升，血浆离子钙0.17±0.01毫克/分升，两者p均小于0.001）。尽管血浆钙增加，但在输注PTH期间尿钙排泄率保持不变。注射PTH后，对照大鼠的血浆骨化三醇水平（257±18皮克/毫升）高于肾衰竭大鼠（162±5皮克/毫升，p小于0.001）。用50纳克骨化三醇静脉预处理肾衰竭大鼠可纠正对PTH的异常钙调节反应。为了排除PTH对肠道钙吸收的影响，在禁食18小时的动物中进行PTH输注。肾衰竭大鼠（血浆钙0.37±0.04毫克/分升，血浆离子钙0.20±0.01毫克/分升）和对照大鼠（血浆钙0.37±0.03毫克/分升，血浆离子钙0.19±0.01）在输注PTH后的钙增加不再有差异，这表明两组动物之间骨骼对钙的动员相似。我们得出结论，在这个肾衰竭模型中，对PTH的钙调节反应受损的机制是肠道对PTH缺乏反应，而不是骨骼抵抗。
