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Circulating Levels of Dickkopf-Related Protein 1 Decrease as Measured GFR Declines and Are Associated with PTH

Corey M Forster1,2, Christine A White2, Mandy E Turner1

  • 1Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.

American Journal of Nephrology
|November 25, 2020
PubMed
Summary

Dickkopf-related protein 1 (DKK1) and sclerostin levels change oppositely as kidney function declines in chronic kidney disease (CKD). DKK1 decreased with worsening kidney function and was linked to parathyroid hormone (PTH).

Keywords:
Dickkopf-related protein 1Mineral bone disease in chronic kidney diseaseParathyroid hormoneSclerostinWnt/β-catenin

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Area of Science:

  • Nephrology
  • Endocrinology
  • Bone Metabolism

Background:

  • The Wnt/β-catenin pathway is crucial in adynamic bone disease development in early chronic kidney disease (CKD).
  • Dickkopf-related protein 1 (DKK1) and sclerostin, Wnt/β-catenin pathway antagonists, are potential but underutilized clinical indicators for bone disease.
  • This study investigates DKK1 and sclerostin levels across a spectrum of kidney function.

Purpose of the Study:

  • To characterize the levels of DKK1, sclerostin, and other mineral metabolism biomarkers.
  • To examine the association of these biomarkers with kidney function (measured by glomerular filtration rate - GFR).

Main Methods:

  • Measured inulin-clearance GFR (mGFR) in 90 participants.
  • Assessed circulating levels of DKK1, sclerostin, FGF-23, PTH, calcium, phosphate, α-klotho, and vitamin D metabolites.
  • Employed Spearman correlations and linear regressions to analyze associations.

Main Results:

  • DKK1 levels decreased (r = 0.6, p < 0.001) and sclerostin increased (r = -0.4, p < 0.001) as kidney function declined.
  • Both DKK1 and sclerostin correlated with phosphate, PTH, FGF-23, and 1,25-dihydroxyvitamin D3.
  • DKK1 remained significantly associated with PTH after adjusting for age and mGFR.

Conclusions:

  • DKK1 and sclerostin exhibit opposing trends with declining kidney function.
  • DKK1 levels significantly decrease with reduced GFR and show an independent association with PTH.
  • Further research is needed to evaluate the utility of Wnt signaling inhibitors in predicting bone health outcomes in CKD patients.