Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability

Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability.BackgroundDespite 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.MethodsRats (N = 5 per group) underwent renal ischemia for 30minutes, 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 96hours 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.ResultsPVP was significantly (P < 0.05) increased at 24hours and peaked at 48hours after IRI compared with shams as well as baseline levels. PVP after IRI became similar to shams after 96hours. This correlated with increases in blood urea nitrogen and creatinine at similar time points. At 48hours, 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.ConclusionsIncreased 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