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.