Tipping the redox balance of oxidative stress in fibrogenic pathways in chronic kidney disease

Daryl M. Okamura, Jonathan Himmelfarb

Patients with moderate to advanced chronic kidney disease or end-stage renal disease have a greatly increased cardiovascular risk that cannot be explained entirely by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation have been proposed as nontraditional cardiovascular risk factors in this patient population. Oxidative stress reflects the redox balance between oxidant generation and antioxidant mechanisms. The generation of reactive oxygen species is not simply a random process that oxidizes nearby macromolecules, but, in many instances, the oxidants target particular amino acid residues or lipid moieties. Oxidant mechanisms are now recognized to be intimately involved in cell signaling and to be vital components of the immune response. This is equally true for antioxidant mechanisms as well. In the progression of chronic kidney disease, the redox balance is not in equilibrium and is tipped toward oxidation, resulting in the dysregulation of cellular process and subsequent tissue injury. In this review we discuss the major oxidant and antioxidant pathways and the biomarkers to assess redox status. We also review the data linking the pathogenesis of oxidative stress, inflammation, and the progressive loss of kidney function in chronic kidney disease.