Circulating Sclerostin and Dickkopf-1 (DKK1) in Predialysis Chronic Kidney Disease (CKD): Relationship With Bone Density and Arterial Stiffness

Calcif Tissue Int. 2012 Jun;90(6):473-80. doi: 10.1007/s00223-012-9595-4. Epub 2012 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density
  • Bone Morphogenetic Proteins / blood*
  • Bone Morphogenetic Proteins / metabolism
  • Bone Remodeling
  • Dialysis
  • Female
  • Genetic Markers
  • Glomerular Filtration Rate
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Vascular Calcification / pathology
  • Vascular Stiffness*
  • Wnt Signaling Pathway

Substances

  • Bone Morphogenetic Proteins
  • DKK1 protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • SOST protein, human