title: Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability.
abstract: BACKGROUND
  Despite the advent of dialysis, survival with acute renal failure when associated with multiorgan failure is poor. The development of lung injury after shock or visceral ischemia has been shown; however, the effects of isolated renal ischemia/reperfusion injury (IRI) on the lungs are unclear. We hypothesized that isolated renal IRI could alter pulmonary vascular permeability (PVP) and that macrophages could be important mediators in this response.
  
  
  METHODS
  Rats (N = 5 per group) underwent renal ischemia for 30 minutes, followed by reperfusion. Lung vascular permeability was evaluated by quantitation of Evans blue dye extravasation from vascular space to lung parenchyma at 1, 24, 48, or 96 hours after reperfusion. Serum was collected for blood urea nitrogen and creatinine at each time point. To examine the role of the macrophage, the macrophage pacifant CNI-1493, which inhibits the release of macrophage-derived inflammatory products, was administered in a blinded fashion during renal IRI.
  
  
  RESULTS
  PVP was significantly (P < 0.05) increased at 24 hours and peaked at 48 hours after IRI compared with shams as well as baseline levels. PVP after IRI became similar to shams after 96 hours. This correlated with increases in blood urea nitrogen and creatinine at similar time points. At 48 hours, CNI-1493 significantly abrogated the increase in PVP compared with IRI alone. However, CNI-1493 did not alter the course of the acute renal failure. Pulmonary histology demonstrated interstitial edema, alveolar hemorrhage, and red blood cell sludging after renal IRI, which was partially attenuated by CNI-1493.
  
  
  CONCLUSIONS
  Increased PVP develops after isolated renal IRI, and macrophage-derived products are mediators in this response. These findings have implications for understanding the mechanisms underlying respiratory dysfunction associated with acute renal failure.
authors.affiliation: Nephrology Division, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Kramer
authors.forename: G
authors.initials: G
authors.lastname: Postler
authors.forename: K F
authors.initials: KF
authors.lastname: Salhab
authors.forename: C
authors.initials: C
authors.lastname: Mendez
authors.forename: L C
authors.initials: LC
authors.lastname: Carey
authors.forename: H
authors.initials: H
authors.lastname: Rabb
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D006835:Hydrazones / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000293:injuries* / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D055370:Lung Injury; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*; D000813:Anilides; D006146:Guanidines
chemical_list: D016207:Cytokines; D006835:Hydrazones; C097256:semapimod; D000813:Anilides; D006146:Guanidines