Antonsen J E, Sherrard D J, Andress D L
Department of Medicine, Veterans Affairs Medical Center, Seattle, Washington, USA.
Kidney Int. 1998 Jan;53(1):223-7. doi: 10.1046/j.1523-1755.1998.00735.x.
The control of hyperparathyroidism in patients with chronic renal failure continues to be a problem, particularly when parathyroid hormone (PTH) suppression becomes refractory to calcitriol activation of parathyroid cell 1,25-dihydroxyvitamin D receptors. To evaluate whether parathyroid cell calcium receptor activation may be useful in suppressing PTH levels, we tested the safety and effectiveness of a novel calcimimetic agent in dialysis patients with hyperparathyroidism. In a prospective, dose finding study, the calcimimetic agent, NPS R-568, was administered orally to seven patients at the start of a hemodialysis session and again 24 hours later. Plasma PTH, calcitonin and ionized calcium levels were measured over a 48 hour period and patients were observed for adverse events. Plasma PTH levels fell abruptly in all patients after a single dose of the compound, with the maximum suppression occurring within one to two hours after its administration. Following the administration of low doses (40 or 80 mg), the suppressed PTH levels rose to baseline values over 48 hours, whereas in patients who received high doses (120 or 200 mg) the mean PTH level remained 51% below baseline. Plasma calcitonin increased after the administration of both low and high doses (peak effect within 4 to 6 hr), with levels always returning to baseline by 48 hours. There were no episodes of hypocalcemia and no adverse effects were reported. We conclude that the activation of parathyroid cell calcium receptors by a novel calcimimetic compound is safe and effective in acutely suppressing PTH secretion in dialysis patients with hyperparathyroidism. Whether concomitant stimulation of calcitonin secretion will provide added beneficial effects on bone remodeling remains to be determined in long-term studies.
慢性肾衰竭患者甲状旁腺功能亢进的控制仍然是一个问题，尤其是当甲状旁腺激素（PTH）抑制对甲状旁腺细胞1,25 - 二羟维生素D受体的骨化三醇激活变得难治时。为了评估甲状旁腺细胞钙受体激活是否有助于抑制PTH水平，我们测试了一种新型拟钙剂在患有甲状旁腺功能亢进的透析患者中的安全性和有效性。在一项前瞻性剂量探索研究中，在血液透析开始时给7名患者口服拟钙剂NPS R - 568，并在24小时后再次给药。在48小时内测量血浆PTH、降钙素和离子钙水平，并观察患者的不良事件。所有患者在单次服用该化合物后血浆PTH水平均急剧下降，最大抑制作用在给药后1至2小时内出现。服用低剂量（40或80毫克）后，被抑制的PTH水平在48小时内升至基线值，而接受高剂量（120或200毫克）的患者中，平均PTH水平仍比基线低51%。低剂量和高剂量给药后血浆降钙素均升高（4至6小时内达到峰值效应），且水平在48小时时总是恢复到基线。未发生低钙血症事件，也未报告不良反应。我们得出结论，一种新型拟钙剂激活甲状旁腺细胞钙受体在急性抑制患有甲状旁腺功能亢进的透析患者的PTH分泌方面是安全有效的。降钙素分泌的伴随刺激是否会对骨重塑产生额外的有益影响仍有待长期研究确定。
