title: Morphologic and functional renal impact of acute kidney injury after prolonged hemorrhagic shock in mice.
abstract: OBJECTIVE
  Sparse data are available on renal consequences of hemorrhagic shock in mice. This study aimed to extend the current knowledge on functional and morphologic renal impact of hemorrhagic shock in mice and to determine its ability to stand as an accurate model of acute kidney injury.
  
  
  METHODS
  In vivo study.
  
  
  METHODS
  University research unit.
  
  
  METHODS
  C57/Bl6 mice.
  
  
  METHODS
  A model of controlled hemorrhagic shock was adapted to determine the renal impact of hemorrhagic shock in mice.
  
  
  RESULTS
  Renal functions and kidney morphology were followed up from 3 hrs to 21 days after hemorrhagic shock. When prolonged up to 2 hrs, hypotension (35 mm Hg mean arterial blood pressure) induced by temporary blood removal was responsible for an early and lasting increase in hypoxia-inducible factor-1α and kidney-inducible molecule-1 gene expression that paralleled acute tubular necrosis and renal failure. Two-hr hypotension induced an important but reversible decrease in glomerular filtration rate up to 6 days after hemorrhagic shock. Other renal dysfunctions included a renal loss of sodium, assessed by the increase in sodium excretion, and a decrease in urine concentration that persists up to day 21. Tissular damages prevailed in the outer medulla 2 days after hemorrhagic shock, being maximal at day 6. At day 21, renal healing was associated with epithelial recovery and a significant interstitial fibrosis.
  
  
  CONCLUSIONS
  Our data indicate that apparent recovery of renal function after acute kidney injury can mask persisting dysfunctions and tissular damages that could predispose to chronic kidney disease. Prolonged hemorrhagic shock in mice closely mimics renal effects induced by similar situation in humans, thus providing a useful tool to investigate pathophysiological mechanisms and protection strategies against acute kidney injury in situations such as hemorrhagic shock.
authors.affiliation: Département d'Anesthésie Réanimation, Equipe Accueil Inserm 4564 Université Paul Sabatier Toulouse III, CHU Purpan, Toulouse, France. nicolas.mayeur@inserm.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mayeur
authors.forename: Vincent
authors.initials: V
authors.lastname: Minville
authors.forename: Acil
authors.initials: A
authors.lastname: Jaafar
authors.forename: Julien
authors.initials: J
authors.lastname: Allard
authors.forename: Talal
authors.initials: T
authors.lastname: Al Saati
authors.forename: Céline
authors.initials: C
authors.lastname: Guilbeau-Frugier
authors.forename: Olivier
authors.initials: O
authors.lastname: Fourcade
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Girolami
authors.forename: Stéphane
authors.initials: S
authors.lastname: Schaak
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins