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. 2017 May 11;12(5):e0176411.
doi: 10.1371/journal.pone.0176411. eCollection 2017.

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD

Geert J Behets  1 , Liesbeth Viaene  2 , Björn Meijers  2 , Frank Blocki  3 , Vincent M Brandenburg  4 , Anja Verhulst  1 , Patrick C D'Haese  1 , Pieter Evenepoel  2
Affiliations

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD

Geert J Behets et al. PLoS One. .

Abstract

Introduction: Mounting evidence indicates that a disturbed Wnt-β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete.

Methods: We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage 4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls. We investigated associations with demographics, renal function, parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH)2 vitamin D, biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and bone turnover markers.

Results: Serum sclerostin, but not DKK1, increases in more advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH)2 vitamin D concentrations. Bone turnover markers are highest in hemodialysis patients presenting the combination of high PTH with low sclerostin level. Serum DKK1 levels are lower in CKD patients than in controls and are not associated with laboratory parameters of mineral metabolism. Interestingly, a direct association between DKK1 and platelet count was observed.

Conclusion: In CKD, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients. DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet counts.

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Conflict of interest statement

Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: FB is an employee of Diasorin Inc. The funder provided support in the form of salaries for author FB and supplied research materials for the current study. The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The commercial affiliation does not alter the authors' adherence to all PLOS ONE policies on sharing data and material.

Figures

Fig 1
Fig 1. Serum sclerostin (A) and DKK1 (B) levels according to CKD stages and in healthy volunteers (HV).
Fig 2
Fig 2. Correlation between blood platelet count and serum DKK levels in CKD patients not yet on dialysis (R2 = 0.28, p<0.0001, Spearman).
Fig 3
Fig 3. Bone-specific alkaline phosphatase level (Bone ALP) (A) and C-terminal telopeptide of collagen type 1 (CTX-I) (B), categorized according to PTH and sclerostin levels above [high] or below [low] the median.
Groups with same indices differ significantly.
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