Sepsis-induced acute kidney injury.
Sepsis is a common and frequently fatal condition in which mortality has been consistently linked to increasing organ dysfunction. For example, acute kidney injury (AKI) occurs in 40-50% of septic patients and increases mortality six to eight-fold. However, the mechanisms by which sepsis causes organ dysfunction are not well understood and hence current therapy remains reactive and nonspecific.



Recent studies have challenged the previous notion that organ dysfunction is solely secondary to hypoperfusion, by showing, for example, that AKI occurs in the setting of normal or increased renal blood flow; and that it is characterized not by acute tubular necrosis or apoptosis, but rather by heterogeneous areas of colocalized sluggish peritubular blood flow and tubular epithelial cell oxidative stress. Evidence has also shown that microvascular dysfunction, inflammation, and the metabolic response to inflammatory injury are fundamental pathophysiologic mechanisms that may explain the development of sepsis-induced AKI.



The implications of these findings are significant because in the context of decades of negative clinical trials in the field, the recognition that other mechanisms are at play opens the possibility to better understand the processes of injury and repair, and provides an invaluable opportunity to design mechanism-targeted therapeutic interventions.
aCenter for Critical Care Nephrology bDepartment of Critical Care Medicine, The CRISMA Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Hernando
H
Gómez
John A
JA
Kellum
D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology*; D017209:Apoptosis; D015415:Biomarkers; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D012079:Renal Circulation; D018805:Sepsis / Q000150:complications*
D015415:Biomarkers
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