title: Epithelial transport during septic acute kidney injury.
abstract: A goal for scientists studying septic acute kidney injury (AKI) should be to formulate a conceptual model of disease that is able to coherently reconcile the molecular and inflammatory consequences of sepsis with impaired epithelial tubular function, diminished glomerular filtration rate (GFR) and ultimately kidney failure. Recent evidence has shed light on how sepsis modulates the tubular regulation of ion, glucose, urea and water transport and acid-base homeostasis in the kidney. The present review summarizes recent discoveries on changes in epithelial transport under septic and endotoxemic conditions as well as the mechanisms that link inflammation with impaired tubular membrane transport. This paper also proposes that the tubular dysfunction that is mediated by inflammation in sepsis ultimately leads to increased sodium and chloride delivery to the distal tubule and macula densa, contributing to tubuloglomerular feedback and impaired GFR. We feel that this conceptual model resolves many of the physiologic and clinical paradoxes that septic AKI presents to practicing researchers and clinicians.
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976.1 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Morrell
authors.affiliation: The Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA CRISMA (Clinical Research Systems Modeling of Acute Illness) Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976.1 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA The Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hallows
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976.1 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA The Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Núria M
authors.initials: NM
authors.lastname: Pastor-Soler
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D018805:Sepsis / Q000150:complications* / Q000378:metabolism
chemical_list: D002712:Chlorides
keywords: AKI; ion transport; sepsis; toll-like receptor; tubuloglomerular feedback