The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism

Am J Physiol Renal Physiol. 2005 Feb;288(2):F253-64. doi: 10.1152/ajprenal.00302.2004. Epub 2004 Oct 26.

Abstract

Serum calcium levels are regulated by the action of parathyroid hormone (PTH). Major drivers of PTH hypersecretion and parathyroid cell proliferation are the hypocalcemia and hyperphosphatemia that develop in chronic kidney disease patients with secondary hyperparathyroidism (SHPT) as a result of low calcitriol levels and decreased kidney function. Increased PTH production in response to systemic hypocalcemia is mediated by the calcium-sensing receptor (CaR). Furthermore, as SHPT progresses, reduced expression of CaRs and vitamin D receptors (VDRs) in hyperplastic parathyroid glands may limit the ability of calcium and calcitriol to regulate PTH secretion. Current treatment for SHPT includes the administration of vitamin D sterols and phosphate binders. Treatment with vitamin D is initially effective, but efficacy often wanes with further disease progression. The actions of vitamin D sterols are undermined by reduced expression of VDRs in the parathyroid gland. Furthermore, the calcemic and phosphatemic actions of vitamin D mean that it has the potential to exacerbate abnormal mineral metabolism, resulting in the formation of vascular calcifications. Effective new treatments for SHPT that have a positive impact on mineral metabolism are clearly needed. Recent research shows that drugs that selectively target the CaR, calcimimetics, have the potential to meet these requirements.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium / blood*
  • Cholecalciferol / pharmacology
  • Chronic Disease
  • Homeostasis
  • Humans
  • Hyperparathyroidism, Secondary / physiopathology*
  • Kidney Diseases / complications*
  • Receptors, Calcitriol / physiology*
  • Receptors, Calcium-Sensing / physiology*

Substances

  • Receptors, Calcitriol
  • Receptors, Calcium-Sensing
  • Cholecalciferol
  • Calcium