Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis?

Background: Derangements in bone metabolism and vascular calcification (VC) substantially contribute to the accelerated cardiovascular morbidity and mortality in chronic kidney disease (CKD). The Wnt signalling pathway is increasingly recognized to play an important role in bone homeostasis and VC. Circulating levels of the Wnt inhibitor sclerostin are elevated in CKD patients. The present study investigated whether the circulating levels of sclerostin are associated with all-cause mortality in haemodialysis (HD) patients.

Methods: We performed a post-hoc survival analysis in 100 prevalent HD patients (68 ± 13 years, 40 male) recruited in 2006 who were prospectively followed for median 637 (8-1000, range) days. Parameters of mineral metabolism including bone-specific alkaline phosphatase (bsAP) and serum sclerostin were determined in spare blood samples collected at baseline.

Results: Serum concentrations of serum sclerostin amounted to 110 (82-151) [median (iqr)] pmol/L. Patients with sclerostin levels above median were characterized by older age, higher haemoglobin and creatinine level and lower bsAP concentration. During a median follow-up of 637 days, 31 patients died. Higher circulating sclerostin levels were associated with decreased mortality in prevalent HD patients: unadjusted hazard ratio (HR) 0.51 (0.24-1.06) (P = 0.06); HR adjusted for age and gender for serum sclerostin levels above versus below median was 0.33 (0.15-0.73) (P = 0.006). When bsAP was entered in the Cox regression analysis, it replaced sclerostin in the final model.

Conclusions: Our data show that high circulating sclerostin levels are associated with improved survival and suggest that a low bsAP activity may be in the causal pathway.