Enhanced oxidative stress partly resulting from an over-production of superoxide anion (O(2)(•-)) represents a novel and particular risk factor in chronic kidney disease (CKD) patients. This study was therefore designed to evaluate O(2)(•-) determinants in this population. O(2)(•-) production was evaluated using chemiluminescence method in 136 CKD patients (79M/57F, median age: 69.5 [27.4-94.6]). Renal function (evaluated by the glomerular filtration rate using modification of diet in renal disease (MDRD)), inflammation, lipids, nutritional and bone mineral as well as clinical parameters were evaluated. Potential relationships between O(2)(•-) and these clinico-biological parameters were investigated to identify main determinants of such a pathological process. Enhanced O(2)(•-) production has been observed at the pre-dialysis phase: stages 4 and 5 of CKD (p = 0.0065). In multivariate analysis, low eGFR (MDRD <30 mL/min/1.73 m(2); p = 0.046), high fibrinogen (≥3.7 g/L; p = 0.044) and abnormal HDL cholesterol (<1.42 mmol/L and ≥ 1.75 mmol/L; p = 0.042) were the main determinants of O(2)(•-) production in CKD patients.