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

BMC Nephrology

Markus Ketteler²  Christiane Drechsler¹  Ulrich Gladziwa⁶  Sinah Hübner⁷  Georg Mühlenbruch⁴  Leon Schurgers³  Thilo Krüger⁷  Ralf Koos⁵  Rafael Kramann⁷  Vincent M Brandenburg⁵ 

[1] Department of Internal Medicine 1, Division of Nephrology, University of Würzburg, Würzburg, Germany;Department of Nephrology, Klinikum Coburg, Coburg, Germany;Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands;Department of Neuro-Radiology, University Hospital of the RWTH Aachen, Aachen, Germany;Department of Cardiology, University Hospital of the RWTH, Pauwelsstraße 30, D- 52057 Aachen, Germany;Dialysis Center, Kuratorium für Heimdialyse, Würselen, Germany;Department of Nephrology, University Hospital of the RWTH Aachen, Aachen, Germany

关键词: Sclerostin;    Renal osteodystrophy;    Vascular calcification;    Mineral metabolism;    Hemodialysis;    Coronary calcification;    Cardiovascular disease;    Aortic valve disease;   

Others  :  1082820
DOI  :  10.1186/1471-2369-14-219

 received in 2013-06-03, accepted in 2013-10-01,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Brandenburg et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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