title: Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury.
abstract: Acute renal failure (ARF) commonly occurs after whole body ischemia. Most experimental models of ARF have relied on the isolated renal artery clamping model; however, there is a pressing need to develop and understand the pathogenesis of new models with more "clinical relevance." We evaluated a new murine model of ARF after whole body ischemia reperfusion injury (WBIRI). WBIRI was induced by an infusion of potassium chloride and a cardiac arrest period of 10 min. Resuscitation was achieved by cardiac compressions, ventilation, epinephrine, and fluids. WBIRI leads to a significant increase in serum creatinine (SCr) and renal tubular injury by 24 h. Renal myeloperoxidase (MPO) levels increased at 24 h after WBIRI. Increased expression of the proinflammatory genes, ICAM-1 and IL-6, was also observed in the kidney following WBIRI. On the basis of recent data that T cells are important mediators of isolated renal IRI, WBIRI was evaluated in T cell-deficient nu/nu mice. T cell-deficient mice had a significantly reduced rise in SCr and decreased tubular injury compared with wild-type mice. T cell-deficient mice had a decrease in ICAM-1 expression after WBIRI, but no decrease in renal MPO. This study describes a new, clinically relevant, model of ARF after WBIRI in mice and identifies the T cell as an important mediator of renal injury following WBIRI. Reduced ICAM-1 expression may provide a mechanism for this involvement.
authors.affiliation: Department of Medicine and Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Burne-Taney
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.forename: Naoko
authors.initials: N
authors.lastname: Yokota
authors.forename: Myron
authors.initials: M
authors.lastname: Weisfeldt
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Traystman
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase