Tags

Type your tag names separated by a space and hit enter

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD.
PLoS One. 2017; 12(5):e0176411.Plos

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.

Authors+Show Affiliations

University of Antwerp, Dept. Biomedical Sciences, Laboratory of Pathophysiology, Wilrijk, Belgium.KUL Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium.KUL Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium.DiaSorin, Inc., Stillwater, Minnesota, United States of America.University Hospital RWTH Aachen, Department of Cardiology, Aachen, Germany.University of Antwerp, Dept. Biomedical Sciences, Laboratory of Pathophysiology, Wilrijk, Belgium.University of Antwerp, Dept. Biomedical Sciences, Laboratory of Pathophysiology, Wilrijk, Belgium.KUL Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28493902

Citation

Behets, Geert J., et al. "Circulating Levels of Sclerostin but Not DKK1 Associate With Laboratory Parameters of CKD-MBD." PloS One, vol. 12, no. 5, 2017, pp. e0176411.
Behets GJ, Viaene L, Meijers B, et al. Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. PLoS One. 2017;12(5):e0176411.
Behets, G. J., Viaene, L., Meijers, B., Blocki, F., Brandenburg, V. M., Verhulst, A., D'Haese, P. C., & Evenepoel, P. (2017). Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. PloS One, 12(5), e0176411. https://doi.org/10.1371/journal.pone.0176411
Behets GJ, et al. Circulating Levels of Sclerostin but Not DKK1 Associate With Laboratory Parameters of CKD-MBD. PLoS One. 2017;12(5):e0176411. PubMed PMID: 28493902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. AU - Behets,Geert J, AU - Viaene,Liesbeth, AU - Meijers,Björn, AU - Blocki,Frank, AU - Brandenburg,Vincent M, AU - Verhulst,Anja, AU - D'Haese,Patrick C, AU - Evenepoel,Pieter, Y1 - 2017/05/11/ PY - 2017/01/03/received PY - 2017/04/09/accepted PY - 2017/5/12/entrez PY - 2017/5/12/pubmed PY - 2017/9/12/medline SP - e0176411 EP - e0176411 JF - PloS one JO - PLoS One VL - 12 IS - 5 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28493902/Circulating_levels_of_sclerostin_but_not_DKK1_associate_with_laboratory_parameters_of_CKD_MBD_ L2 - https://dx.plos.org/10.1371/journal.pone.0176411 DB - PRIME DP - Unbound Medicine ER -