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Morphologic and functional renal impact of acute kidney injury after prolonged hemorrhagic shock in mice*

Mayeur, Nicolas MD; Minville, Vincent MD, PhD; Jaafar, Acil MD; Allard, Julien MD; al Saati, Talal PhD; Guilbeau-Frugier, Céline MD; Fourcade, Olivier MD, PhD; Girolami, Jean Pierre PhD; Schaak, Stéphane PhD; Tack, Ivan MD, PhD

doi: 10.1097/CCM.0b013e31821f04f0
Laboratory Investigations

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.

Design: In vivo study.

Setting: University research unit.

Subjects: C57/Bl6 mice.

Interventions: A model of controlled hemorrhagic shock was adapted to determine the renal impact of hemorrhagic shock in mice.

Measurements and Main 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.

Département d'Anesthésie Réanimation (NM,VM, OF, SC), Equipe Accueil Inserm 4564 Université Paul Sabatier Toulouse III, CHU Purpan, Toulouse, France; Laboratoire de physiologie and Inserm U858 (NM, VM, AJ, JA, JPG, SS, IT), CHU Rangueil Université toulouse III, Toulouse, France; Unité Inserm 563 (TAS), CHU Purpan, Toulouse, France; and Service d'anatomopathologie (CGF), CHU Rangueil, Toulouse, France.

This work was supported by a grant from the Académie Nationale de Médecine to Dr. Mayeur.

The authors have not disclosed any potential conflicts of interest.

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins