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Circulating Wnt/β-catenin signalling inhibitors and uraemic vascular calcifications.
- Source :
-
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2015 Aug; Vol. 30 (8), pp. 1356-63. Date of Electronic Publication: 2015 Mar 27. - Publication Year :
- 2015
-
Abstract
- Background: The process of vascular calcification has been associated with the canonical Wnt/β-catenin signalling pathway in cell cultures and animal studies. The relationship between circulating Wnt/β-catenin inhibitors and vascular calcification in dialysis patients is unknown. The aim of this study was to investigate the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signalling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in dialysis patients.<br />Methods: This was a prospective observational cohort study. One hundred and twenty-five patients on maintenance haemodialysis participated in the study. Serum levels of Dkk-1 and sclerostin were measured. AoC scores were calculated from plain films of both posterior-anterior and lateral views. The patients were followed up for 2 years or until death or withdrawal.<br />Results: The circulating sclerostin level was inversely associated with the severity of AoC (P = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, P = 0.008) and intact parathyroid hormone (r = -0.523, P < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), P = 0.015] after adjusting for a propensity score. In contrast, serum Dkk-1 was not associated with AoC and clinical outcomes.<br />Conclusions: In long-term haemodialysis patients, circulating sclerostin but not Dkk-1 is inversely associated with AoCs and future cardiovascular events. Our findings suggest that sclerostin, as a bone-related protein, might act as a communicator between uraemic bone and vasculature.<br /> (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing
Cardiovascular Diseases etiology
Cross-Sectional Studies
Female
Genetic Markers
Humans
Male
Middle Aged
Parathyroid Hormone blood
Prospective Studies
Uremia etiology
Vascular Calcification etiology
Wnt Signaling Pathway
Biomarkers blood
Bone Morphogenetic Proteins blood
Cardiovascular Diseases blood
Intercellular Signaling Peptides and Proteins blood
Renal Dialysis adverse effects
Uremia blood
Vascular Calcification blood
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2385
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- Publication Type :
- Academic Journal
- Accession number :
- 25817223
- Full Text :
- https://doi.org/10.1093/ndt/gfv043