title: Restoring the physiology of vitamin D receptor activation and the concept of selectivity.
abstract: Abnormalities of bone mineral parameters (calcium, phosphate, vitamin D, and parathyroid hormone) are nearly always present in patients with chronic kidney disease (CKD). These typically consist of hypocalcemia, hyperphosphatemia, abnormalities of vitamin D metabolism, and secondary hyperparathyroidism, and are now defined as CKD mineral bone disorders (CKD-MBD). Currently, emerging evidence indicates that deficiencies in vitamin D receptor (VDR) activation play crucial roles in adversely affecting the cardiovascular health of CKD patients. VDRs are not restricted to skeletal tissue, but are instead widely expressed throughout the body at several sites, such as in cardiac tissue, vascular smooth muscle cells, endothelial cells, renal tissue, and cells of the immune system. Restoring the physiology and modulation of VDR activator levels results in correlative regulatory effects on mineral homeostasis, hypertension, cardiovascular disease, and vascular calcification, as well as a number of other endpoints in cardiac and renal pathology. Among the compounds available for treatment of CKD-MBD, paricalcitol is a selective VDR activator. The term 'selective' refers to paricalcitol being more selective in affecting VDR pathways in the parathyroid gland compared with bone and intestine. As such, paricalcitol's selectivity allows for a wider therapeutic window with effects beyond parathyroid hormone control and mineral management, and may explain, in part, the increased survival advantage with paricalcitol treatment.
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Irene
authors.initials: I
authors.lastname: Brenna
authors.forename: Elisa
authors.initials: E
authors.lastname: Volpi
authors.forename: Paola
authors.initials: P
authors.lastname: Ciceri
authors.forename: Florjan
authors.initials: F
authors.lastname: Mehmeti
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004872:Ergocalciferols / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology; D018167:Receptors, Calcitriol / Q000502:physiology*
chemical_list: D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol