The methylguanidine-to-creatinine ratio, serum NOx concentrations, and vascular disease in nondiabetic hemodialysis patients

Abstract

Background. Hemodialysis (HD) patients are in a highly oxidative state, which may contribute to accelerated atherosclerosis. Methylguanidine (MG) and lipid peroxides may be used as markers of the oxidative status in HD patients. A recent study demonstrated the non-enzymatic generation of nitric oxide (NO) via a reaction between hydrogen peroxide and arginine. We determined the relationships between serum concentrations of the oxidation products of NO (NOx) and oxidative status markers, and the relationships between these markers and the prevalence of atherosclerotic disease in HD patients. Methods. We measured serum concentrations of MG, creatinine (Cr), NOx, and thiobarbituric acid reactive substances (TBARS), and determined the presence of apparent vascular disease in 324 nondiabetic HD patients. Results. The MG concentration, but not the NOx concentration, was correlated with the Cr concentration (r ϭ 0.64; P Ͻ 0.001). Based on simple linear regression analysis, the NOx concentration (r ϭ 0.13; P Ͻ 0.05) correlated with the MG/Cr ratio, but did not correlate with the TBARS concentration. Multiple linear regression analysis revealed that the serum NOx concentration (r ϭ 0.13; P Ͻ 0.01) and the duration of dialysis (r ϭ 0.13; P ϭ 0.05) correlated with the MG/Cr ratio. There were no significant differences in the concentrations of NOx, TBARS, or the MG/Cr ratio between HD patients with and without vascular disease. Multivariate logistic regression analysis showed that only age and hypertension were independent risk factors for prevalent vascular disease. Conclusions. These results suggest that non-enzymatic synthesis of NO via oxidative stress may occur in HD patients. However, the serum markers of oxidation status at any one single moment may not correlate with the prevalence of apparent vascular disease in HD patients.

Nuclear Magnetic Resonance–Based Metabolomics of Human Filtered Serum: A Great White Hope in Appraisal of Chronic Stable Angina and Myocardial Infarction

“…The increased level of MG in CSA patients as compared to NC is suggestive of increased oxidation of creatinine with hydroxyl radicals via creatol (15,18). Studies have also demonstrated a correlation between serum creatinine and MG levels, which supports the idea of the oxidative stress of disease (15,16).…”

“…Two independent approaches measured one constituent and found that similar observations further validated the precision of the results. An augmented level of creatinine may help MG production causing neutrophils stimulation through free radicals, cytokines, and other peroxides (15)(16)(17) and supports the idea of oxidative stress of the disease, as explained above in detail.…”

“…........................................................................................................... injury-causing myocardial ischemia-reperfusion and the generation of oxidative stress from the activation of metabolic pathways by RIP (23). Arginine was significantly augmented in CSA and MI compared to NC, which again establishes the role of oxidative stress in CAD and the formation of nitric oxide through enzymatic or nonenzymatic pathways (16). Another study revealed the capacity of L-arginine to lessen necrotic injury in an experimental model of myocardial ischemia plus reperfusion.…”

“…Oxidative stress plays a major role in the pathophysiology of CAD (15). CSA is a kind of apoptosis-based cell death phenomenon (15,16). In CSA, the ischemia-reperfusion phenomenon causes the release of free radicals, cytokines, and other proinflammatory mediators (15).…”