Wetmore James B, Quarles L Darryl
Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Nat Clin Pract Nephrol. 2009 Jan;5(1):24-33. doi: 10.1038/ncpneph0977. Epub 2008 Oct 28.
Considerable advances have been made in the understanding of the pathogenesis and treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). These include the discovery that the calcium-sensing receptor has an important role in the regulation of parathyroid gland function, the development of calcimimetics to target this receptor, the recognition that vitamin D receptor activation has important functions beyond the regulation of mineral metabolism, the identification of the phosphaturic factor fibroblast growth factor 23 and the contribution of this hormone to disordered phosphate and vitamin D metabolism in CKD. However, despite the availability of calcimimetics, phosphate binders, and vitamin D analogs, control of SHPT remains suboptimal in many patients with advanced kidney disease. In this Review, we explore several unresolved issues regarding the pathogenesis and treatment of SHPT. Specifically, we examine the significance of elevated circulating fibroblast growth factor 23 levels in CKD, question the proposition that calcitriol deficiency is truly a pathological state, explore the relative importance of the vitamin D receptor and the calcium-sensing receptor in parathyroid gland function and evaluate the evidence to support the treatment of SHPT with calcimimetics and vitamin D analogs. Finally, we propose a novel treatment framework in which calcimimetics are the primary therapy for suppressing parathyroid hormone production in patients with end-stage renal disease.
在慢性肾脏病（CKD）继发性甲状旁腺功能亢进（SHPT）的发病机制和治疗的理解方面已经取得了相当大的进展。这些进展包括发现钙敏感受体在甲状旁腺功能调节中起重要作用、开发靶向该受体的拟钙剂、认识到维生素D受体激活在矿物质代谢调节之外具有重要功能、鉴定磷尿因子成纤维细胞生长因子23以及该激素对CKD中磷酸盐和维生素D代谢紊乱的作用。然而，尽管有拟钙剂、磷结合剂和维生素D类似物，但在许多晚期肾病患者中，SHPT的控制仍然不理想。在本综述中，我们探讨了关于SHPT发病机制和治疗的几个未解决问题。具体而言，我们研究了CKD中循环成纤维细胞生长因子23水平升高的意义，质疑骨化三醇缺乏是否真的是一种病理状态，探讨维生素D受体和钙敏感受体在甲状旁腺功能中的相对重要性，并评估支持用拟钙剂和维生素D类似物治疗SHPT的证据。最后，我们提出了一种新的治疗框架，其中拟钙剂是终末期肾病患者抑制甲状旁腺激素产生的主要治疗方法。
