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

Vincent M. Brandenburg*, Rafael Kramann, Ralf Koos, Thilo Krueger, Leon Schurgers, Georg Muehlenbruch, Sinah Huebner, Ulrich Gladziwa, Christiane Drechsler, Markus Ketteler

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

115 Citations (Web of Science)

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.
Original languageEnglish
Article number219
JournalBmc Nephrology
Volume14
DOIs
Publication statusPublished - 10 Oct 2013

Keywords

  • Aortic valve disease
  • Cardiovascular disease
  • Coronary calcification
  • Hemodialysis
  • Mineral metabolism
  • Vascular calcification
  • Renal osteodystrophy
  • Sclerostin

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