The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism
The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism
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DOI：
10.1681/asn.v1341017
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发表时间：
2002-04-01
影响因子：
13.6
通讯作者：
Coburn, JW
中科院分区：
文献类型：
--
作者：
Goodman, WG;Hladik, GA;Coburn, JW
在许多终末期肾病继发性甲状旁腺功能亢进症患者中，维生素D类固醇治疗可以降低血浆甲状旁腺激素(PTH)，但在治疗过程中往往会出现高钙血症、高磷血症或两者兼而有之。因此，需要替代的治疗方法来管理过量的甲状旁腺素分泌。拟钙剂通过激活甲状旁腺中的钙感受器直接抑制甲状旁腺激素的分泌，但临床经验有限。52例继发性甲状旁腺功能亢进的血液透析患者单次口服拟钙剂AMG073，剂量从5到100 mg，或安慰剂。血浆甲状旁腺素水平在25、50、75或100 mg剂量后2小时下降，最大降幅分别为43+/-29%、40+/-36%、54+/-28%或55+/-39%。服用大于或等于25毫克剂量的所有患者的血浆甲状旁腺素水平均降低，但服用安慰剂的患者血浆甲状旁腺素水平没有变化。在每天服用25或50 mg AMG073的患者中，治疗8d后，血浆甲状旁腺素水平在前3~4d下降，并在治疗8d后保持在基线水平以下。服用50 mg AMG073 8d的患者血清钙浓度也比治疗前下降了5%至10%，但在接受较低剂量的患者中，血钙浓度没有变化。AMG 073治疗后，血清磷水平和钙磷离子乘积的值均降低。因此，AMG 073治疗8天有效地降低了血浆甲状旁腺素水平，改善了与软组织和血管钙化有关的矿物质代谢紊乱，并改善了终末期肾病患者的不良心血管结局。
Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcernia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of greater than or equal to25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.