Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation and vascular disease in the spectrum of advanced chronic kidney disease

BACKGROUND: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. AIMS: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. METHODS: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intimamedia thickness and atherosclerotic plaques were assessed by ultrasonography. RESULTS: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intimamedia thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, Creactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). CONCLUSIONS: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.