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Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Shunsuke Yamada1, Cecilia M Giachelli1

  • 1Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

Bone
|November 17, 2016
PubMed

Insights

Vascular calcification (VC) is common in chronic kidney disease (CKD). FGF23 and α-Klotho may impact VC, with α-Klotho showing a protective role, potentially offering new therapeutic avenues for CKD-mineral and bone disorder.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Vascular calcification (VC) is prevalent in aging, diabetes mellitus, and chronic kidney disease (CKD), significantly predicting cardiovascular morbidity and mortality in CKD patients.
  • Pathological mechanisms of VC include vascular smooth muscle cell osteochondrogenic differentiation, apoptosis, extracellular vesicle release, and elastin degradation.
  • Elevated serum phosphate in CKD accelerates mineral deposition in the vasculature and heart valves.

Purpose of the Study:

  • To investigate the roles of α-Klotho and fibroblast growth factor 23 (FGF23) in the pathogenesis of uremic vascular calcification (VC) within the context of CKD-mineral and bone disorder (CKD-MBD).
  • To clarify the conflicting reports on FGF23's effects on VC and consolidate evidence for α-Klotho's protective role.
  • To identify potential therapeutic targets by evaluating the interplay of phosphate, FGF23, and α-Klotho in VC.

Main Methods:

  • Review and synthesis of existing literature on vascular calcification, CKD-MBD, FGF23, and α-Klotho.
  • Analysis of discordant and supporting evidence regarding the effects of FGF23 and α-Klotho on VC.
  • Exploration of the systemic interplay between phosphate, FGF23, and α-Klotho in VC pathogenesis.

Main Results:

  • Evidence suggests FGF23 has discordant effects on VC, requiring further investigation.
  • Mounting evidence supports a protective role for α-Klotho in vascular calcification.
  • Further research is needed to elucidate the synthesis and precise roles of FGF23 and α-Klotho in normal and diseased states.

Conclusions:

  • α-Klotho demonstrates a protective role against vascular calcification, offering a potential therapeutic target.
  • Further elucidation of FGF23's role and the combined action of FGF23 and α-Klotho is crucial for understanding uremic VC.
  • Systemic evaluation of phosphate, FGF23, and α-Klotho interactions may yield novel therapeutic strategies for CKD-MBD patients.

Keywords:
Chronic kidney diseaseFibroblast growth factor 23Vascular calcificationα-Klotho

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