The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine

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.

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.

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.

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.