High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study

Abstract

Background: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover, and it plays a role in cardiovascular calcification processes. Previous findings indicate that sclerostin regulation is disturbed in chronic kidney disease (CKD). The aim of this study was to assess the association of circulating sclerostin levels with mortality in dialysis patients.

Methods: From a prospective cohort study of incident dialysis patients in the Netherlands, all patients with measured circulating sclerostin at 3 months after the start of dialysis (baseline) were included in the present analysis: n = 673, age 63 ± 14 years, mean serum sclerostin (ELISA) 1.24 ± 0.57 ng/mL. By Cox regression analyses, we assessed the association of sclerostin levels with cardiovascular and non-cardiovascular mortality both in the short (18 months) and long term (4-year follow-up).

Results: Serum sclerostin levels in the entire cohort correlated with intact parathyroid hormone levels (r = -0.25, P < 0.001), age (r = 0.16, P < 0.001) and serum alkaline phosphatase (r = -0.13, P = 0.001). After adjustment for various clinical and biochemical parameters, patients in the highest sclerostin tertile had a significantly lower risk of cardiovascular death [hazard ratio 0.29, 95% confidence interval (CI) 0.13-0.62] and for all-cause mortality (0.39, 95% CI 0.22-0.68) within 18 months compared with patients of the lowest tertile. The association of sclerostin levels with outcome was less pronounced for long-term cardiovascular mortality and absent for non-cardiovascular mortality.

Conclusions: High levels of serum sclerostin are associated with lower short-term cardiovascular mortality in dialysis patients. The exact mechanisms of this association, e.g. how sclerostin influences or reflects uraemic vascular calcification, need to be investigated in further studies.

Keywords: CKD-MBD; end-stage renal disease; mortality; renal osteodystrophy; sclerostin.