title: Sepsis-associated AKI: epithelial cell dysfunction.
abstract: Acute kidney injury (AKI) occurs frequently in critically ill patients with sepsis, in whom it doubles the mortality rate and half of the survivors suffer permanent kidney damage or chronic kidney disease. Failure in the development of viable therapies has prompted studies to better elucidate the cellular and molecular etiologies of AKI, which have generated novel theories and paradigms for the mechanisms of this disease. These studies have shown multifaceted origins and elements of AKI that, in addition to/in lieu of ischemia, include the generation of damage-associated molecular patterns and pathogen-associated molecular patterns, the inflammatory response, humoral and cellular immune activation, perturbation of microvascular flow and oxidative stress, bioenergetic alterations, cell-cycle alterations, and cellular de-differentiation/re-differentiation. It is becoming clear that a major etiologic effector of all these inputs is the renal tubule epithelial cell (RTEC). This review discusses these elements and their effects on RTECs, and reviews the current hypotheses of how these effects may determine the fate of RTECs during sepsis-induced AKI.
authors: Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
authors: David R
authors: DR
authors: Emlet
authors: Department of Anesthesia, Vanderbilt University School of Medicine, Nashville, TN.
authors: Andrew D
authors: AD
authors: Shaw
authors: Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address: kellumja@ccm.upmc.edu.
authors: John A
authors: JA
authors: Kellum
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007686:Kidney Tubules, Distal / Q000166:cytology; D007687:Kidney Tubules, Proximal / Q000166:cytology; D018384:Oxidative Stress; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
keywords: DAMPs and PAMPs; Sepsis; acute kidney injury; renal tubule epithelial cell