Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study

BMC Nephrol. 2013 Oct 10;14:219. doi: 10.1186/1471-2369-14-219.

Abstract

Background: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients.

Methods: We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR).

Results: CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves.

Conclusion: We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aortic Valve
  • Bicuspid Aortic Valve Disease
  • Biomarkers / blood
  • Bone Morphogenetic Proteins / blood*
  • Calcinosis / blood*
  • Calcinosis / etiology
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / etiology
  • Cross-Sectional Studies
  • Female
  • Genetic Markers
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / etiology
  • Heart Valve Diseases / blood*
  • Heart Valve Diseases / etiology
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / rehabilitation*
  • Male
  • Middle Aged
  • Renal Dialysis*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Statistics as Topic
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human