title: A role for oxidative stress.
abstract: The pathogenesis of sepsis-induced acute kidney injury (AKI) is not fully understood, and may involve altered systemic hemodynamics and renal circulation, renal hypoxia and perhaps direct tubular toxicity. Oxidative stress, induced by systemic and intrarenal generation of reactive oxygen species (ROS) can directly exert renal parenchymal damage and may intensify renal microvascular and functional dysregulation, with a feedforward loop of hypoxia and ROS generation. Herein we review compelling evidence that sepsis is associated with systemic and intrarenal intense oxidative and nitrosative stress with a depletion of antioxidant capacity. Inflammation and tissue hypoxia conceivably play a central role in the generation of ROS in the septic patient. Though oxidative and nitrosative stress are likely to participate in the pathogenesis of sepsis-induced AKI, it is impossible to clearly identify their isolated independent role and renal-specific effect since there are complex interactions involved linking various affected organs, ROS generation with altered systemic hemodynamics, compromised microcirculation, hypoxia and distorted cellular function. Facing this complex disease entity, alleviation of oxidative stress single-handedly is unlikely to be effective in the prevention of sepsis-associated renal dysfunction. However, the addition of antioxidants to a comprehensive treatment strategy seems a reasonable approach.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Heyman
authors.forename: Seymour
authors.initials: S
authors.lastname: Rosen
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenberger
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000150:complications* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D005978:Glutathione