title: Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.
abstract: Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.affiliation: Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, 'Grigore T. Popa' University of Medicine, Iasi, Romania.
authors.forename: Dimitrie
authors.initials: D
authors.lastname: Siriopol
authors.affiliation: Department of Radiology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Hilmi Umut
authors.initials: HU
authors.lastname: Unal
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Karaman
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gezer
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Kilinc
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.affiliation: Department of Biochemistry, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Ahmet Kerem
authors.initials: AK
authors.lastname: Guler
authors.affiliation: Department of Biochemistry, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: İbrahim
authors.initials: İ
authors.lastname: Aydin
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.affiliation: Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, 'Grigore T. Popa' University of Medicine, Iasi, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
authors.affiliation: Nephrology and Hypertension Department, IIS-Fundacion Jimenez Diaz and School of Medicine, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Division of Nephrology, Department of Medicine, Koc University School of Medicine, Topkapi, 03490, Istanbul, Turkey. drkanbay@yahoo.com.
authors.forename: Mehmet
authors.identifier: 0000-0002-1297-0675
authors.initials: M
authors.lastname: Kanbay
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000150:complications; D002318:Cardiovascular Diseases / Q000209:etiology*; D059168:Carotid Intima-Media Thickness; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D053244:Osteoprotegerin
keywords: Biomarker; Cardiovascular disease; Inflammation; Kidney disease; Osteoprotegerin