Uremic toxicity and sclerostin in chronic kidney disease patients

Background and aims. - Sclerostin is a circulating inhibitor of the Wnt/beta-catenin pathway and may have a role in chronic kidney disease (CKD)-mineral and bone disorder. Blood sclerostin levels are known to be elevated in patients undergoing maintenance dialysis. The aims of the present study were to evaluate sclerostin levels in patients at different CKD stages and study potential associations between sclerostin levels and (i) biochemical parameters that are disturbed in CKD, (ii) markers of vascular disease and (iii) mortality. Methods. - One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry tests and assays for sclerostin, protein-bound uremic toxins (indoxylsulphate [IS] and p-cresyl sulphate [PCS]) and the toxin 132 microglobulin (beta 2M) were performed. Aortic and coronary calcification and arterial stiffness were assessed by multislice spiral computed tomography and pulse wave velocity measurements. The enrolled patients were prospectively monitored for mortality. Results. - Sclerostin levels were found to be elevated in CKD patients (especially those on hemodialysis). Furthermore, sclerostin levels were positively correlated with inflammation markers, phosphate, fibroblast growth factor 23, IS, PCS, beta 2M and arterial stiffness. A multivariate linear regression analysis indicated that sclerostin levels were independently associated with IS, PCS and beta 2M levels. Elevated serum sclerostin appeared to be associated with mortality (independently of age and inflammation). However, this association disappeared after adjustment for a propensity score including age, phosphate, interleukin-6, CKD stage and PCS. Conclusion. - Our results indicate that sclerostin levels are elevated in CKD patients and are associated with inflammation, vascular lesions, uremia and (potentially) mortality. (C) 2014 Association Societe de nephrologie. Published by Elsevier Masson SAS. All rights reserved.