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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-122070
  • 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 toBackground: 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.show moreshow less

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Metadaten
Author: Vincent M. Brandenburg, Rafael Kramann, Ralf Koos, Thilo Krueger, Leon Schurgers, Georg Mühlenbruch, Sinah Hübner, Ulrich Gladziwa, Christiane Drechler, Markus Ketteler
URN:urn:nbn:de:bvb:20-opus-122070
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Language:English
Parent Title (English):BMC Nephrology
ISSN:1471-2369
Year of Completion:2013
Volume:14
Issue:219
Source:BMC Nephrology 2013, 14:219. doi:10.1186/1471-2369-14-219
DOI:https://doi.org/10.1186/1471-2369-14-219
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:GLA protein UCMGP; aortic valve; aortic valve disease; bone formation; calcium; cardiovascular disease; computed tomography; coronary calcification; coronary-artery calcification; fetuin A; hemodialysis; kidney-disease CKD; mineral metabolism; mortality; renal osteodystrophy; risk factors; sclerostin; vascular calcification
Release Date:2016/02/23
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung