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

Autor:	Forster CM; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada.; Department of Medicine, Queen's University, Kingston, Ontario, Canada., White CA; Department of Medicine, Queen's University, Kingston, Ontario, Canada., Turner ME; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada., Norman PA; Kingston General Health Research Institute, Kingston General Hospital, Kingston, Ontario, Canada., Ward EC; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada., Hopman WM; Kingston General Health Research Institute, Kingston General Hospital, Kingston, Ontario, Canada.; Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada., Adams MA; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada., Holden RM; Department of Biomedical and Molecular Science, Queen's University, Kingston, Ontario, Canada, rachel.holden@kingstonhsc.ca.; Department of Medicine, Queen's University, Kingston, Ontario, Canada, rachel.holden@kingstonhsc.ca.
Jazyk:	angličtina
Zdroj:	American journal of nephrology [Am J Nephrol] 2020; Vol. 51 (11), pp. 871-880. Date of Electronic Publication: 2020 Nov 25.
DOI:	10.1159/000511658
Abstrakt:	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. (© 2020 S. Karger AG, Basel.)
Databáze:	MEDLINE
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