title: Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure.
abstract: Chronic kidney disease (CKD) causes alterations in mineral metabolism inducing the development of secondary hyperparathyroidism (HPT) and renal osteodystrophy. Recently, it has been suggested that these alterations play an important role in determining extraskeletal calcification and thus cardiovascular morbidity and mortality among CKD patients. An impaired 1 alfa -hydroxylation of 25-hydroxycholecalciferol (25(OH)D3) to 1,25-dihydroxycholecalciferol (1,25(OH)2 D3) with decreased circulating 1,25(OH)2 D3 levels is commonly observed in patients with creatinine clearance below 70 ml/min. The reduction in 1,25(OH)2 D3 production triggers the up-regulation of parathyroid hormone (PTH) synthesis, through a decreased suppression on PTH gene transcription and a decreased intestinal calcium absorption. A reduced expression of vitamin D receptor (VDR) and a less efficient binding of the complex 1,25(OH)2 D3 -VDR to specific DNA segments account for the resistance to 1,25(OH)2 D3 in target cells. Thus, absolute and relative 1,25(OH)2 D3 deficiency is one of the causes of secondary HPT in patients with CKD, together with phosphate retention and skeletal resistance to PTH. Consistently with these pathophysiological mechanisms, the therapeutic use of 1,25(OH)2 D3 still represents a milestone for the treatment of secondary HPT and renal osteodystrophy, even though hypercalcemia and hyperphosphatemia are common adverse events and may increase the risk of cardiovascular calcifications. To reduce the impact of such adverse effects while retaining anti-PTH activity, 1,25(OH)2 D3 analogues with lower calcemic effects have been synthesized and are now available for clinical use.
authors.affiliation: Renal Division, S. Paolo Hospital, Milan-Italy. mariocozzolino@hotmail.com
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gallieni
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.forename: Teresa
authors.initials: T
authors.lastname: Arcidiacono
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vezzoli
mesh_terms: D002114:Calcinosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003404:Creatinine / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D054559:Hyperphosphatemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D; D003404:Creatinine; D002118:Calcium