TY  - JOUR
A1  - Brandenburg, Vincent M.
A1  - Kramann, Rafael
A1  - Koos, Ralf
A1  - Krueger, Thilo
A1  - Schurgers, Leon
A1  - Mühlenbruch, Georg
A1  - Hübner, Sinah
A1  - Gladziwa, Ulrich
A1  - Drechler, Christiane
A1  - Ketteler, Markus
T1  - Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study
JF  - BMC Nephrology
N2  - 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.
KW  - coronary calcification
KW  - cardiovascular disease
KW  - aortic valve disease
KW  - calcium
KW  - mortality
KW  - sclerostin
KW  - aortic valve
KW  - bone formation
KW  - computed tomography
KW  - fetuin A
KW  - risk factors
KW  - GLA protein UCMGP
KW  - kidney-disease CKD
KW  - coronary-artery calcification
KW  - hemodialysis
KW  - mineral metabolism
KW  - vascular calcification
KW  - renal osteodystrophy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122070
SN  - 1471-2369
VL  - 14
IS  - 219
ER  -