title: Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.
abstract: OBJECTIVE
  Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population.
  
  
  METHODS
  A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively
  
  
  RESULTS
  The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values).
  
  
  CONCLUSIONS
  Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.
authors.affiliation: Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey. Electronic address: drkanbay@yahoo.com.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kanbay
authors.affiliation: Department of Medicine, Division of Nephrology, Konya Numune State Hospital, Konya, Turkey.
authors.forename: Baris
authors.initials: B
authors.lastname: Afsar
authors.affiliation: Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, Romania; 'Grigore T. Popa' University of Medicine, Iasi, Romania.
authors.forename: Dimitrie
authors.initials: D
authors.lastname: Siriopol
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 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: Mustafa
authors.initials: M
authors.lastname: Gezer
authors.affiliation: Department of Biochemistry, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Taş
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.affiliation: Department of Radiology, 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: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.affiliation: Koc University School of Medicine, Ankara, Turkey.
authors.forename: Kayhan
authors.initials: K
authors.lastname: Tarim
authors.affiliation: Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002423:Cause of Death; D003920:Diabetes Mellitus / Q000453:epidemiology; D043169:Endostatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D012307:Risk Factors; D016019:Survival Analysis; D014421:Turkey
chemical_list: D043169:Endostatins
keywords: Cardiovascular events; Chronic kidney disease; Endostatin; Endothelial dysfunction