Serum Sclerostin and Adverse Outcomes in Nondialyzed Chronic Kidney Disease Patients

Autor: Adrian Covic, Yusuf Oguz, Hilmi Umut Unal, Yasemin Gulcan Kurt, Mutlu Saglam, Hakki Cetinkaya, Mehmet Kanbay, Tayfun Eyileten, David Goldsmith, Dimitrie Siriopol, Gabriel Veisa, Abdulgaffar Vural, Mahmut Gok, Mahmut Ilker Yilmaz, Murat Karaman, Sebahattin Sari
Rok vydání: 2014
Předmět:
Adult
Genetic Markers
Male
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Population
Renal function
Kaplan-Meier Estimate
urologic and male genital diseases
Biochemistry
Bone remodeling
chemistry.chemical_compound
Endocrinology
Predictive Value of Tests
Renal Dialysis
Risk Factors
Chronic kidney disease-mineral and bone disorder
Internal medicine
medicine
Humans
Renal Insufficiency
Chronic
education
Adaptor Proteins
Signal Transducing
Proportional Hazards Models
Univariate analysis
education.field_of_study
business.industry
Biochemistry (medical)
Middle Aged
medicine.disease
female genital diseases and pregnancy complications
Fibroblast Growth Factors
Vasodilation
Fibroblast Growth Factor-23
Cholesterol
chemistry
Cardiovascular Diseases
Predictive value of tests
Bone Morphogenetic Proteins
Multivariate Analysis
Sclerostin
Female
Endothelium
Vascular
business
Biomarkers
Glomerular Filtration Rate
Kidney disease
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 99:E1854-E1861
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2014-2042
Popis: The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population.Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values.Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P.001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients.This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.
Databáze: OpenAIRE
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