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拟钙剂用于治疗继发性甲状旁腺功能亢进:十年证据综述

The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10 Year Evidence Review.

作者信息

Rodríguez Mariano, Goodman William G, Liakopoulos Vassilios, Messa Piergiorgio, Wiecek Andrzej, Cunningham John

机构信息

Servicio de Nefrologia, IMIBIC, Hospital Universitario Reina Sofia, Córdoba, Spain.

Amgen, Inc., Thousand Oaks, California.

出版信息

Semin Dial. 2015 Sep-Oct;28(5):497-507. doi: 10.1111/sdi.12357. Epub 2015 Mar 8.

DOI:10.1111/sdi.12357
PMID:25752650
Abstract

Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds.

摘要

在拟钙剂被发现之前,继发性甲状旁腺功能亢进症(SHPT)的治疗完全依赖于使用磷结合剂、维生素D衍生物或进行甲状旁腺切除术,但效果有限。拟钙剂的治疗应用,以及对钙敏感受体(CaSR)在甲状旁腺功能生理调节中关键作用的更深入理解,极大地推动了透析实践中甲状旁腺功能亢进症的管理。拟钙剂选择性地与甲状旁腺组织中的CaSR受体结合,增强细胞外钙离子对甲状旁腺激素(PTH)分泌的抑制作用,从而即使在血清钙浓度正常或较低时也能降低PTH水平。临床可用的拟钙剂开启了SHPT患者管理的新时代。事实上,拟钙剂化合物已被证明可降低所有形式甲状旁腺功能亢进症(包括原发性甲状旁腺功能亢进症(PHPT)和甲状旁腺癌)中的PTH水平并降低血清钙浓度。这些发现强调了CaSR作为这类临床疾病治疗靶点的至关重要性。正在研发新型拟钙剂,与目前可用的拟钙剂化合物相比,它们有可能提供更高的疗效和安全性。

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