title: Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Division of Nephrology, Istanbul Medeniyet University School of Medicine, Istanbul, Turkey 34000; Department of Nephrology (D.S., G.V., A.C.), Gr. T.Popa University of Medicine and Pharmacy, Iasi, Romania 700115; Departments of Radiology (M.S, S.S.), Biochemistry (Y.G.K.), and Nephrology (M.G., H.C., M.I.Y., H.U.U., Y.O., T.E., A.V.), Gülhane School of Medicine, Ankara, Turkey 06018; Department of Nephrology (D.G.), Guy's Hospital, King's Health Partners, London, United Kingdom SE1 7EH, and Department of Medicine (M.K.), Division of Nephrology University School of Medicine, Instanbul, Turkey 34450.
authors: Mehmet
authors: M
authors: Kanbay
authors: Dimitrie
authors: D
authors: Siriopol
authors: Mutlu
authors: M
authors: Saglam
authors: Yasemin Gulcan
authors: YG
authors: Kurt
authors: Mahmut
authors: M
authors: Gok
authors: Hakki
authors: H
authors: Cetinkaya
authors: Murat
authors: M
authors: Karaman
authors: Hilmi Umut
authors: HU
authors: Unal
authors: Yusuf
authors: Y
authors: Oguz
authors: Sebahattin
authors: S
authors: Sari
authors: Tayfun
authors: T
authors: Eyileten
authors: David
authors: D
authors: Goldsmith
authors: Abdulgaffar
authors: A
authors: Vural
authors: Gabriel
authors: G
authors: Veisa
authors: Adrian
authors: A
authors: Covic
authors: Mahmut Ilker
authors: MI
authors: Yilmaz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005819:Genetic Markers; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D014664:Vasodilation / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002784:Cholesterol