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Updated: Nov 28, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Circulating Levels of Dickkopf-Related Protein 1 Decrease as Measured GFR Declines and Are Associated with PTH Levels
Corey M Forster1,2, Christine A White2, Mandy E Turner1
1Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.
Background:
The Wnt/β-catenin pathway has been implicated in the development of adynamic bone disease in early-stage chronic kidney disease (CKD). Dickkopf-related protein 1 (DKK1) and sclerostin are antagonists of the Wnt/β-catenin pathway yet have not been widely used as clinical indicators of bone disease. This study characterized levels of DKK1, sclerostin, and other biomarkers of mineral metabolism in participants across a spectrum of inulin-measured glomerular filtration rate (GFR).
Methods:
GFR was measured by urinary inulin clearance (mGFR) in 90 participants. Blood samples were obtained for measurement of circulating DKK1, sclerostin, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphate, α-klotho, and vitamin D metabolites including 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. Spearman correlations and linear regressions were used where appropriate to examine the associations between measured values.
Results:
The median [IQR] age was 64 years [53.0-71.0], and the median [IQR] mGFR was 32.6 [21.7-60.6] mL/min. DKK1 decreased (r = 0.6, p < 0.001) and sclerostin increased (r = -0.4, p < 0.001) as kidney function declined, and both were associated with phosphate, PTH, FGF-23, and 1,25-dihydroxyvitamin D3 in the unadjusted analysis. After adjustment for age and mGFR, DKK1 remained significantly associated with PTH.
Conclusion:
The results of this study demonstrate opposing trends in Wnt/β-catenin pathway inhibitors, DKK1 and sclerostin, as mGFR declines. Unlike sclerostin, DKK1 levels decreased significantly as mGFR declined and was independently associated with PTH. Future studies should determine whether measurement of Wnt signaling inhibitors may be useful in predicting bone histomorphometric findings and important clinical outcomes in patients with CKD.
Insights
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).
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.
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