Molecular biology of Vitamin D: Genomic and nongenomic actions of Vitamin D in chronic kidney disease

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations

Abstract

Chronic kidney disease (CKD) progression is characterized by features of accelerated aging (bone loss, increased propensity for fractures and vascular calcification, hypertension and cardiovascular disease) and a risk of mortality 20- to 30-fold higher than in age- and gender-matched individuals with normal renal function. The progressive loss of renal capacity to maintain the functional integrity of the vitamin D endocrine system is a main determinant of the severe pro-aging features that reduce survival. The goal of this chapter is an update of the progress of the last 5 years in our understanding of the molecular pathophysiology underlying CKD-induced abnormalities in: (a) Systemic and local vitamin D bioactivation to its hormonal form, 1,25-dihydroxyvitamin D or calcitriol; (b) Classical genomic and non-genomic actions of the calcitriol/vitamin D receptor (VDR) complex that compromise survival, and (c) Synergistic VDR activation by calcitriol and its precursor, 25-hydroxyvitamin D, to counteract VDR reductions. Special focus is directed to the molecular bases supporting the paradigm switch to maximize calcitriol/VDR anti-aging actions. Specifically, from suppression of the PTH gene to attenuate the bone loss predisposing to vascular calcification, to the induction of the FGF23 and α-klotho genes to simultaneously control the pro-aging effects of hyperphosphatemia and of an excess of active vitamin D, while maintaining the plethora of anti-aging/pro-survival actions of renal and circulating klotho. Special attention is also directed into calcitriol/VDR distinct control of Wnt/Β- - catenin signals to promote mineralization in bone while preventing calcification in the vasculature, and into the emerging fields of calcitriol/VDR regulation of microRNA synthesis and klotho-independent anti-aging actions. This mechanistic knowledge is a mandatory first step to evaluate the accuracy of current biomarkers of disease severity and response to therapy.

Original languageEnglish
Title of host publicationVitamin D in Chronic Kidney Disease
PublisherSpringer International Publishing
Pages51-74
Number of pages24
ISBN (Electronic)9783319325071
ISBN (Print)9783319325057
DOIs
StatePublished - Jan 1 2016

Keywords

  • 1,25-dihydroxyvitamin D
  • FGF23
  • Klotho
  • Mortality
  • Parathyroid hyperplasia
  • Vascular calcification
  • Vitamin D receptor

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