Bone and Mineral Disorders Clinic, Division of Nephrology, Children's Mercy Hospital, University of Missouri at Kansas City, 2401Gillham Road, Kansas City, MO, 64108, USA.
Renal Research Laboratory, Research and Development, Kansas City VA Medical Center, Kansas City, MO, 64128, USA.
Pediatr Nephrol. 2019 Mar;34(3):413-422. doi: 10.1007/s00467-018-3935-1. Epub 2018 Mar 19.
The calcium-sensing receptor (CaSR) plays an important role in the homeostasis of serum ionized calcium by regulating parathyroid hormone (PTH) secretion and tubular calcium handling. Calcimimetics, which act by allosteric modulation of the CaSR, mimic hypercalcemia resulting in suppression of PTH release and increase in calciuria. Mostly used in children to treat secondary hyperparathyroidism associated with advanced renal failure, we have shown that calcimimetics can also be successfully used in children with bone and mineral disorders in which elevated PTH plays a detrimental role in skeletal pathophysiology in the face of normal kidney function. The current review briefly discusses the role of the CaSR and calcimimetics in calcium homeostasis, and then addresses the potential applications of calcimimetics in children with normal kidney function with disorders in which suppression of PTH is beneficial.
钙敏感受体(CaSR)通过调节甲状旁腺激素(PTH)的分泌和肾小管钙处理来发挥重要作用,维持血清离子钙的稳态。钙敏感受体变构调节剂通过变构调节 CaSR,模拟高钙血症,从而抑制 PTH 释放和增加尿钙排泄。钙敏感受体变构调节剂主要用于治疗儿童晚期肾衰竭相关的继发性甲状旁腺功能亢进症,我们已经表明,钙敏感受体变构调节剂也可成功用于骨和矿物质疾病的儿童,其中 PTH 升高在正常肾功能情况下对骨骼病理生理学产生有害作用。目前的综述简要讨论了 CaSR 和钙敏感受体变构调节剂在钙稳态中的作用,然后讨论了钙敏感受体变构调节剂在抑制 PTH 有益的肾功能正常的儿童中应用的潜力。