title: Circulating sclerostin and Dickkopf-1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness.
abstract: Abnormalities of bone metabolism and increased vascular calcification are common in chronic kidney disease (CKD) and important causes of morbidity and mortality. The Wnt signaling pathway may play a role in the bone and vascular disturbances seen in CKD, termed collectively "CKD-MBD." The aim of the study was to investigate the possible association of circulating concentrations of the secreted Wnt signaling inhibitors DKK1 and sclerostin with BMD and arterial stiffness in predialysis CKD. Seventy-seven patients (48 M, 29 F), mean age 57 (SD = 14) years with CKD stages 3B (n = 32) and 4 (n = 45) were studied. Sclerostin, DKK1, PTH, and 1,25(OH)(2)D were analyzed. BMD was measured at the lumbar spine (LS), femoral neck (FN), total hip (TH), and forearm (FARM). Arterial stiffness index was determined by contour analysis of digital volume pulse (SI(DVP)). There was a positive correlation between sclerostin and age (r = 0.47, p < 0.000). Sclerostin was higher in men than women (p = 0.013). Following correction for age and gender, there was a negative association between GFR and sclerostin (p = 0.002). We observed a positive association between sclerostin and BMD at the LS (p = 0.0001), FN (p = 0.004), and TH (p = 0.002). In contrast, DKK1 was negatively associated with BMD at the FN (p = 0.038). A negative association was seen between DKK1 and SI(DVP) (p = 0.027). Our data suggest that the Wnt pathway may play a role in CKD-MBD. Prospective studies are required to establish the clinical relevance of sclerostin and DKK1 as serological markers in CKD.
authors.affiliation: Department of Clinical Chemistry, St Thomas' Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Thambiah
authors.forename: R
authors.initials: R
authors.lastname: Roplekar
authors.forename: P
authors.initials: P
authors.lastname: Manghat
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: D
authors.initials: D
authors.lastname: Goldsmith
authors.forename: Geeta
authors.initials: G
authors.lastname: Hampson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000378:metabolism; D016723:Bone Remodeling; D003956:Dialysis; D005260:Female; D005819:Genetic Markers; D005919:Glomerular Filtration Rate; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D061205:Vascular Calcification / Q000473:pathology; D059289:Vascular Stiffness; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human