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

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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)2D 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 (SIDVP). 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 SIDVP (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.

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Acknowledgments

This work was supported by a small grant from the Friends of Guy’s Hospital, London, UK.

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Authors and Affiliations

  1. Department of Clinical Chemistry, St Thomas’ Hospital, London, UK

    S. Thambiah, R. Roplekar, P. Manghat & Geeta Hampson

  2. Osteoporosis Clinic, Guy’s Hospital, London, UK

    S. Thambiah, P. Manghat, I. Fogelman & Geeta Hampson

  3. Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    S. Thambiah

  4. Department of Nuclear Medicine, Guy’s Hospital, London, UK

    I. Fogelman

  5. Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich, UK

    W. D. Fraser

  6. Renal Unit, Guy’s Hospital, London, UK

    D. Goldsmith

  7. Department of Chemical Pathology, St Thomas’ Hospital, 5th Floor, North Wing, Lambeth Palace Road, London, SE1 7EH, UK

    Geeta Hampson

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Correspondence to Geeta Hampson.

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Thambiah, S., Roplekar, R., Manghat, P. et al. Circulating Sclerostin and Dickkopf-1 (DKK1) in Predialysis Chronic Kidney Disease (CKD): Relationship with Bone Density and Arterial Stiffness. Calcif Tissue Int 90, 473–480 (2012). https://doi.org/10.1007/s00223-012-9595-4

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  • DOI: https://doi.org/10.1007/s00223-012-9595-4

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