Relevance of oxidative pathways in the pathophysiology of chronic kidney disease.
Patients with uremia (whether requiring renal replacement therapy or not) have a greatly increased cardiovascular risk that cannot be explained entirely by traditional cardiovascular risk factors. An increase in oxidative stress has been proposed as a nontraditional cardiovascular risk factor in this patient population. Using a wide variety of different biomarkers of increased oxidative stress status, numerous laboratories around the world have now unequivocally demonstrated that uremia is a state of increased oxidative stress. Recent data also suggest linkages between oxidative stress inflammation, endothelial dysfunction, and malnutrition in the uremic population. These factors are probably synergistic in their effects on atherogenecity and risk of a cardiovascular event. The pathophysiology of increased oxidative stress in uremia is multifactorial, but the retention of oxidized solute by the loss of kidney function is probably a major contributor. Uremic oxidative stress can be characterized biologically by an increase in lipid per oxidation products and reactive aldehyde groups as well as by increased retention of oxidized thiols. Two recently published studies have suggested that antioxidative therapy may be particularly promising in reducing cardiovascular events in this patient population.Further definitive studies of antioxidant use are greatly needed.
Himmelfarb
Jonathan
J
Division of Nephrology and Transplantation, Maine Medical Center, 22 Bramhall Street, Portland, ME 04102, USA. himmej@mmc.org
D000210:Acute-Phase Reaction / Q000150:complications; D000975:Antioxidants / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D044342:Malnutrition / Q000150:complications; D018384:Oxidative Stress / Q000502:physiology*; D006435:Renal Dialysis
D000975:Antioxidants