ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO0517

Bone Expression of Sclerostin in CKD and Dialysis Patients

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Laster, Marciana, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Pereira, Renata C., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Albrecht, Lauren V., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Salusky, Isidro B., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
Background

Sclerostin, a 22-kDa glycoprotein secreted by osteocytes, negatively regulates bone formation through the inhibition of the Wnt/β-Catenin pathway. In patients with CKD, circulating sclerostin correlates negatively with bone formation but the impact of bone expression of sclerostin requires further investigation.

Methods

87 pediatric patients with CKD underwent iliac crest bone biopsy with the quantification of sclerostin bone expression using immunohistochemistry (IHC). Subjects with circulating sclerostin values at the upper and lower extremes of each population (n=6 CKD and n=6 dialysis) underwent staining with two β-catenin antibodies that recognize the phosphorylated/unphosphorylated states.

Results

The median (IQR) age of the cohort was 17 (14, 20) and 39% had pre-dialysis CKD (Table). Significant correlations between IHC sclerostin and bone histomorphometry were limited to the dialysis group: IHC sclerostin correlated with bone formation rate (r=-0.34, p=0.02) and osteoid thickness (r=-0.3, p=0.03). In the sub-group undergoing β -catenin staining, dialysis patients demonstrated low bone staining of sclerostin independent of circulating sclerostin. CKD subjects with high circulating sclerostin levels (ranging from 58 to 110 pmol/L) demonstrated increased sclerostin staining in osteocytes when compared with CKD patients with lower serum sclerostin (ranging from 30 to 36 pmol/L). Phosphorylated β -catenin staining was higher and unphosphorylated β -catenin levels lower in bone tissues with high circulating sclerostin.

Conclusion

Together, these data support a model whereby high levels of circulating sclerostin from osteocytes contributes to altered bone remodeling through aberrant Wnt signaling activity in CKD and may provide a rationale to target therapeutic strategies using monoclonal antibodies towards sclerostin.

Funding

  • NIDDK Support