Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification.
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.
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Abdul Rashid
AR
Qureshi
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Hannes
H
Olauson
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Anna
A
Witasp
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Mathias
M
Haarhaus
Department of Cardiology, University Hospital RWTH Aachen, Aachen, Germany.
Vincent
V
Brandenburg
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Annika
A
Wernerson
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Bengt
B
Lindholm
Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden.
Magnus
M
Söderberg
Division of Transplantation Surgery, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Lars
L
Wennberg
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Louise
L
Nordfors
Division of Radiology, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Jonaz
J
Ripsweden
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Barany
Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Stenvinkel