The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine.
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.
Yilmaz
Mahmut Ilker
MI
Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
Saglam
Mutlu
M
Caglar
Kayser
K
Cakir
Erdinc
E
Sonmez
Alper
A
Ozgurtas
Taner
T
Aydin
Ahmet
A
Eyileten
Tayfun
T
Ozcan
Omer
O
Acikel
Cengizhan
C
Tasar
Mustafa
M
Genctoy
Gultekin
G
Erbil
Kemal
K
Vural
Abdulgaffar
A
Zoccali
Carmine
C
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
D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D003300:Copper; D001120:Arginine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D015032:Zinc