Linking oxidative stress and inflammation in kidney disease: which is the chicken and which is the egg?

For end-stage renal disease (ESRD) patients, cardiovascular disease remains the single most common cause of excess morbidity and mortality. Furthermore, although the prevalence of traditional cardiovascular risk factors is high in the dialysis population, the extent and severity of associated cardiovascular morbidity and mortality remain disproportionate to traditional risk factor profiles. Consequently, considerable effort has been focused on "nontraditional" risk factors for cardiovascular events in this patient population. Among the examined nontraditional risk factors, increased oxidative stress as well as increased acute phase inflammation are postulated to be important contributors to uremic cardiovascular risk. Additional important uremic cardiovascular risk factors include malnutrition and endothelial dysfunction, both of which may be directly linked to the processes that cause increased oxidative stress and inflammation in uremia. In this context I review available data linking the pathogenesis of oxidative stress to acute phase inflammation and uremia. I also review data suggesting that oxidative stress in uremia directly contributes to the development of acute phase inflammation and that patients with higher levels of inflammation have higher levels of oxidative stress biomarkers. Similarly I review emerging data on the potential effects of antioxidant therapy on inflammatory biomarkers, as well as data suggesting that strategies to lower acute phase inflammation may also improve biomarkers of oxidative stress. Theoretical constructs evaluating the linkage of oxidative stress and inflammation in uremia and their contribution to the pathogenesis of atherosclerosis are suggested.