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Circulating Wnt/β-catenin signalling inhibitors and uraemic vascular calcifications
- Source :
- Nephrology Dialysis Transplantation. 30:1356-1363
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 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. 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. 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. 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.
- Subjects :
- Genetic Markers
Male
medicine.medical_specialty
medicine.medical_treatment
Signal transduction inhibitor
chemistry.chemical_compound
Renal Dialysis
Internal medicine
medicine
Humans
Prospective Studies
Vascular Calcification
Wnt Signaling Pathway
Adaptor Proteins, Signal Transducing
Uremia
Transplantation
Proportional hazards model
business.industry
Hazard ratio
Wnt signaling pathway
Middle Aged
Cross-Sectional Studies
Endocrinology
chemistry
Cardiovascular Diseases
Parathyroid Hormone
Nephrology
Bone Morphogenetic Proteins
Intercellular Signaling Peptides and Proteins
Sclerostin
Female
Hemodialysis
Animal studies
Aortic valve calcification
business
Biomarkers
Subjects
Details
- ISSN :
- 14602385 and 09310509
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Nephrology Dialysis Transplantation
- Accession number :
- edsair.doi.dedup.....007098429314ab908db28d02f689272d