title: Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study.
abstract: It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change.
  
  
  
  We aimed to determine the nature and extent of changes in renal structure and function over time in an ovine model of septic shock.
  
  
  
  Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes.
  
  
  
  Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy.
  
  
  
  In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.
authors.affiliation: 1 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia.|2 Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Matthew J
authors.identifier: 0000-0003-4345-3213
authors.initials: MJ
authors.lastname: Maiden
authors.affiliation: 3 Department of Pathology, SA Pathology, Adelaide, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Otto
authors.affiliation: 3 Department of Pathology, SA Pathology, Adelaide, Australia.
authors.forename: John K
authors.initials: JK
authors.lastname: Brealey
authors.affiliation: 1 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia.|2 Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Finnis
authors.affiliation: 1 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia.|2 Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: 4 Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Gilles Plains, Australia; and.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Kuchel
authors.affiliation: 2 Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Coralie H
authors.initials: CH
authors.lastname: Nash
authors.affiliation: 1 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Edwards
authors.affiliation: 5 University of Melbourne, Parkville, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology; D000818:Animals; D001706:Biopsy; D001794:Blood Pressure; D002302:Cardiac Output; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D012079:Renal Circulation; D012756:Sheep; D012772:Shock, Septic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
keywords: acute kidney injury; animal models; histology; pathophysiology