Abstract
BackgroundPrevious clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD.MethodsThis retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression.ResultsBaseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022–1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612–0.900, p = 0.002) levels were independent predictors of all-cause mortality.ConclusionsSclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.
Highlights
Previous clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD)
Cardiovascular disease is the leading cause of mortality in patients undergoing maintenance hemodialysis (MHD), with a prevalence 3–10 times higher in such patients compared with the general population [1, 2]
Pelletier et al [8] found that serum sclerostin levels are higher in CKD patients compared with the general population, and start to increase in CKD stage III
Summary
Previous clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). This study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD. Cardiovascular disease is the leading cause of mortality in patients undergoing maintenance hemodialysis (MHD), with a prevalence 3–10 times higher in such patients compared with the general population [1, 2]. Higher cardiovascular risk in patients undergoing MHD is partly explained by chronic kidney disease-mineral. Dysregulated Wnt-β-catenin pathway is involved in cancer, aortic valve calcification, several bone-related phenotypes, and CKD-MBD [4, 5]. In addition to renal retention [9], higher sclerostin in CKD may be related to enhanced production by bone cells [3, 10]. The above findings suggest a role for sclerostin in cardiovascular disease
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