Uremic toxicity, oxidative stress, and hemodialysis as renal replacement therapy.
Patients with uremia are subject to greatly increased cardiovascular risk that cannot be completely explained by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation has been proposed as contributory nontraditional uremic cardiovascular risk factors. Oxidative stress reflects the balance between oxidant generation and antioxidant defense mechanisms. Reduction/oxidation (redox) reactions may result in a stochastic process leading to oxidation of neighboring macromolecules. However, in many instances the reactive oxygen species target particular amino acid residues or lipid moieties. This provides a mechanism by which increased oxidative stress and/or alteration of antioxidant mechanisms can alter cell signaling. In individuals with advanced chronic kidney disease, the redox balance is not in equilibrium and is tipped toward oxidation resulting in the dysregulation of cellular process with subsequent vascular and tissue injury. In this review, the major oxidant and antioxidant pathways and the biomarkers to assess redox status in uremia are discussed, as well as the data linking the pathogenesis of oxidative stress, inflammation, cardiovascular events, and the progressive loss of kidney function in chronic kidney disease.
Himmelfarb
Jonathan
J
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington 98104-2499, USA. himmej@u.washington.edu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D007688:Kidneys, Artificial; D008567:Membranes, Artificial; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects; D012307:Risk Factors; D014511:Uremia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy
D000975:Antioxidants; D015415:Biomarkers; D008567:Membranes, Artificial; D017382:Reactive Oxygen Species