Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure

Mario Cozzolino, Maurizio Gallieni, Diego Brancaccio, Teresa Arcidiacono, Giuseppe Bianchi, Giuseppe Vezzoli

Research output: Contribution to journalArticle

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 α-hydroxylation of 25-hydroxycholecalciferol (25(OH)D3) to 1,25-dihydroxycholecalciferol (1,25(OH)2D3) with decreased circulating 1,25(OH)2D3 levels is commonly observed in patients with creatinine clearance below 70 ml/min. The reduction in 1,25(OH)2D3 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)2D3-VDR to specific DNA segments account for the resistance to 1,25(OH)2D3 in target cells. Thus, absolute and relative 1,25(OH)2D3 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)2D3 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)2D3 analogues with lower calcemic effects have been synthesized and are now available for clinical use.

Original languageEnglish
Pages (from-to)566-577
Number of pages12
JournalJournal of Nephrology
Volume19
Issue number5
Publication statusPublished - Sep 2006

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Keywords

  • Calcium
  • Chronic renal failure
  • Parathyroid hormone
  • Phosphate
  • Vitamin D

ASJC Scopus subject areas

  • Nephrology

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