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Kidney Int. 2015 Dec;88(6):1356-1364. doi: 10.1038/ki.2015.194. Epub 2015 Sep 2.

Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification.

Author information

1
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
2
Department of Cardiology, University Hospital RWTH Aachen, Aachen, Germany.
3
Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden.
4
Division of Transplantation Surgery, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
5
Division of Radiology, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Abstract

Sclerostin, an osteocyte-derived inhibitor of bone formation, is linked to mineral bone disorder. In order to validate its potential as a predictor of vascular calcification, we explored associations of circulating sclerostin with measures of calcification in 89 epigastric artery biopsies from patients with end-stage renal disease. Significantly higher sclerostin levels were found in the serum of patients with epigastric and coronary artery calcification (calcification score 100 or more). In Spearman's rank correlations, sclerostin levels significantly associated with age, intact parathyroid hormone, bone-specific alkaline phosphatase, and percent calcification. Multivariable regression showed that age, male gender, and sclerostin each significantly associated with the presence of medial vascular calcification. Receiver operating characteristic curve analysis showed that sclerostin (AUC 0.68) predicted vascular calcification. Vascular sclerostin mRNA and protein expressions were low or absent, and did not differ between calcified and non-calcified vessels, suggesting that the vasculature is not a major contributor to circulating levels. Thus, high serum sclerostin levels associate with the extent of vascular calcification as evaluated both by coronary artery CT and scoring of epigastric artery calcification. Among circulating biomarkers of mineral bone disorder, only sclerostin predicted vascular calcification.

PMID:
26331407
DOI:
10.1038/ki.2015.194

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