title: The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine.
abstract: BACKGROUND
  Oxidative stress is related to endothelial dysfunction (ED) and cardiovascular outcomes in patients with chronic kidney disease. Increased asymmetric dimethylarginine (ADMA) levels are among the main causes of ED. We aim to investigate any association between ED and ADMA levels, as well as levels of oxidative stress markers, in patients with chronic kidney disease.
  
  
  METHODS
  One hundred fifty-nine patients without diabetes with chronic kidney disease were studied. Staging was performed according to glomerular filtration rate, determined as stages 1 to 5 according to the Kidney Disease Outcomes Quality Initiative (n = 30, 33, 28, 32, and 36, respectively). The control group consisted of 30 healthy subjects. Oxidative stress markers (plasma malondialdehyde [MDA], erythrocyte superoxide dismutase [SOD], glutathione peroxidase [GSH-Px]), trace elements (erythrocyte zinc [EZn], erythrocyte copper [ECu]), plasma selenium (Se), and serum ADMA were studied. Brachial artery endothelium-dependent vasodilatation (FMD) was calculated for all.
  
  
  RESULTS
  FMD, SOD, GSH-Px, EZn, ECu, and Se values were lower, whereas MDA and ADMA levels were higher in patients than controls. Glomerular filtration rate correlated negatively with MDA and ADMA levels and positively with FMD, SOD, and GSH-Px values. These parameters were significantly different among patients with stages 2, 3, 4, and 5 (hemodialysis group; P < 0.001 for all). Regression analysis showed that ADMA (beta = -0.228; P < 0.01), SOD (beta = 0.405; P < 0.001), and oxidized low-density lipoprotein levels (beta = -0.428; P < 0.001) were related independently to FMD, whereas glomerular filtration rate was not involved in the model.
  
  
  CONCLUSIONS
  The present results imply that FMD, oxidative stress, and ADMA levels all are associated with stage of chronic kidney disease. Additionally, levels of oxidative stress markers and ADMA independently determine endothelial function.
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.forename: Kayser
authors.initials: K
authors.lastname: Caglar
authors.forename: Erdinc
authors.initials: E
authors.lastname: Cakir
authors.forename: Alper
authors.initials: A
authors.lastname: Sonmez
authors.forename: Taner
authors.initials: T
authors.lastname: Ozgurtas
authors.forename: Ahmet
authors.initials: A
authors.lastname: Aydin
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.forename: Omer
authors.initials: O
authors.lastname: Ozcan
authors.forename: Cengizhan
authors.initials: C
authors.lastname: Acikel
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tasar
authors.forename: Gultekin
authors.initials: G
authors.lastname: Genctoy
authors.forename: Kemal
authors.initials: K
authors.lastname: Erbil
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology; D002908:Chronic Disease; D003300:Copper / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005919:Glomerular Filtration Rate; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000145:classification / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D012643:Selenium / Q000097:blood; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000097:blood; D014664:Vasodilation / Q000502:physiology; D015032:Zinc / Q000097:blood
chemical_list: D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D003300:Copper; D001120:Arginine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D015032:Zinc