Treatment of secondary hyperparathyroidism: the clinical utility of etelcalcetide.
Treatment of secondary hyperparathyroidism: the clinical utility of etelcalcetide.
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DOI：
10.2147/tcrm.s108490
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发表时间：
2017
影响因子：
2.8
通讯作者：
Bellasi A
中科院分区：
文献类型：
--
作者：
Cozzolino M;Galassi A;Conte F;Mangano M;Di Lullo L;Bellasi A
继发性甲状旁腺功能亢进症 (SHPT) 是一种非常常见、严重且不断恶化的慢性肾脏病并发症，其特征是高血清甲状旁腺激素 (PTH)、甲状旁腺增生和矿物质代谢紊乱。临床上，SHPT 显示肾性骨营养不良、血管钙化、心血管损伤和致命结果。钙敏感受体（CaSR）是PTH分泌的主要生理调节因子；它被钙激活后会迅速抑制 PTH。调节矿物质代谢的另一个重要角色是维生素D受体（VDR），它在维生素D的影响下影响肠道对钙和磷酸盐的吸收、PTH基因表达和骨钙动员。血清磷酸盐水平影响成纤维细胞生长因子 23 (FGF-23) 的产生，这是一种调节血清磷酸盐重吸收、PTH 合成和维生素 D 产生的磷酸钙。目前的治疗方法包括 1) 通过饮食或磷酸盐结合剂控制磷酸盐摄入量，2) 通过 VDR 激活来控制维生素 D，以及 3) 激活 CaSR 的拟钙剂。最近，一种属于拟钙剂类的新型长效肽（etelcalcetide）被批准用于患有SHPT的血液透析患者的静脉注射。 Etelcalcetide 通过硫键直接与 CaSR 结合，抑制甲状旁腺产生和分泌 PTH。大鼠静脉注射后，依替卡赛肽迅速分布至组织并经肾脏消除，而尿毒症动物的非肾脏排泄仅为1.2%。对于血液透析患者，治疗本身是主要的消除途径。 Etelcalcetide 对患有 SHPT 的血液透析患者比安慰剂和西那卡塞更有效，76% 的 etelcalcetide 患者 PTH 降低超过 30%，而安慰剂组为 10%。特别关注药物的安全性；最常见的不良事件是无症状血钙降低，与西那卡塞类似，而胃肠道症状则较少发生。这种有前途的新药可用于更好地控制 SHPT，将与已使用的药物一起优化治疗，使生化参数正常化。
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization. Serum phosphate levels influence fibroblast growth factor 23 (FGF-23) production, a phosphatonin that modulates serum phosphate reabsorption, PTH synthesis, and vitamin D production. Current therapeutic approaches consist of 1) phosphate intake control by diet or phosphate binders, 2) vitamin D by VDR activation, and 3) calcimimetic agents that activate CaSR. Recently, a new long-acting peptide (etelcalcetide) belonging to the calcimimetics class was approved for intravenous use in hemodialysis patients with SHPT. Etelcalcetide binds directly to CaSR, by a sulfide bond, inhibiting the production and secretion of PTH by parathyroid glands. After intravenous administration in rats, etelcalcetide is quickly distributed to the tissues and eliminated by kidneys, while in uremic animals the nonrenal excretion is only 1.2%. In hemodialysis patients, the treatment itself is the main route of elimination. Etelcalcetide in hemodialysis patients with SHPT was more effective than placebo and cinacalcet, with a PTH reduction of >30% in 76% of patients with etelcalcetide versus 10% with placebo. Particular attention was paid to the safety of the drug; the most common adverse event was asymptomatic blood calcium reduction, similar to cinacalcet, while gastrointestinal symptoms were less frequent. This promising new drug available for better control of SHPT will, together with drugs already in use, optimize the treatment to normalize the biochemical parameters.