title: Calcium-sensing receptor activation in chronic kidney disease: effects beyond parathyroid hormone control.
abstract: Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD). Cinacalcet, an allosteric modulator of the calcium-sensing receptor (CaSR) expressed in parathyroid glands, is the only calcimimetic approved to treat SHPT in patients on dialysis. By enhancing CaSR sensitivity for plasma extracellular calcium (Ca(2+)0), cinacalcet reduces serum parathyroid hormone, Ca(2+)0, and serum inorganic phosphorous concentrations, allowing better control of SHPT and CKD-mineral and bone disorders. Of interest, the CaSR also is expressed in a variety of tissues where its activation regulates diverse cellular processes, including secretion, apoptosis, and proliferation. Thus, the existence of potential off-target effects of cinacalcet cannot be neglected. This review summarizes our current knowledge concerning the potential role(s) of the CaSR expressed in various tissues in CKD-related disorders, independently of parathyroid hormone control.
authors.affiliation: Inserm U-1088, University of Picardie Jules Verne, Amiens, France; Division of Nephrology, Ambroise Paré Hospital, Paris-Ile-de-France-Ouest University (University of Versailles Saint-Quentin-En-Yvelines), Paris-Boulogne Billancourt, France. Electronic address: ziad.massy@apr.aphp.fr.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.affiliation: Inserm U-1088, University of Picardie Jules Verne, Amiens, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Hénaut
authors.affiliation: Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institutet, Stockholm, Sweden; Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.affiliation: Department of Nephrology and Institute of Cardiovascular Research VU (Institute for Cardiovascular Research of the Vrije Universiteit of Amsterdam), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
mesh_terms: D001842:Bone and Bones / Q000196:embryology; D057966:Calcimimetic Agents / Q000627:therapeutic use; D000069449:Cinacalcet; D041981:Gastrointestinal Tract / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism; D009281:Naphthalenes / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*; D015398:Signal Transduction; D061205:Vascular Calcification / Q000378:metabolism; D014882:Water-Electrolyte Balance
chemical_list: D057966:Calcimimetic Agents; D009281:Naphthalenes; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet
keywords: Calcium-sensing receptor (CaSR); calcilytics; calcimimetics; chronic kidney disease (CKD); extracellular free ionized calcium (Ca(2+)(0))