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

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.

A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level and Mortality in Maintenance Hemodialysis Patients

“…A second possible explanation for the positive association between sclerostin levels and increased prevalence and severity of vascular calcification may be that the former is lowered as a compensatory mechanism to counterbalance calcification caused by other mechanisms. This may be paradoxically supported by clinical studies that showed a positive association between sclerostin levels and vascular calcification [31,32]. In our study, we observed a U-shaped association between serum sclerostin levels and aortic AoAC, suggesting that 2 nd tertiles of serum sclerostin levels (161 -260 pg/mL) may be associated with the inhibition of vascular calcification.…”

CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease

“…It should also be pointed out that VC might vary depending on arterial type and location along any specific artery. However, we reported a close relation between epigastric artery medial calcification and extent of coronary artery calcification [44]. Finally, since RNA was prepared from a homogenised arterial sample, this precludes any knowledge on how the expression varied between different cell types.…”

Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism

“…It is tempting to hypothesize that this might be caused by greater sclerostin expression and thus explain our findings. On the other hand in the paper by Quershi et al [27], the authors conclude, that plasma sclerostin levels predict the magnitude of vascular calcification, still it is yet unknown if the increased concentrations of sclerostin are the cause, or effect of the increased calcification of the vasculature.…”