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

Background. Despite the advent of dialysis, survival with acute renal failu re when associated with multiorgan failure is poor. The development of lung injury after shock or visceral ischemia has been shown; however, the effec ts of isolated renal ischemia/reperfusion injury (IRI) on the lungs are unc lear. We hypothesized that isolated renal IRI could alter pulmonary vascula r permeability (PVP) and that macrophages could be important mediators in t his response. Methods. Rats (N = 5 per group) underwent renal ischemia for 30 minutes, fo llowed by reperfusion. Lung vascular permeability was evaluated by quantita tion 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 th e 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 a fter IRI became similar to shams after 96 hours. This correlated with incre ases in blood urea nitrogen and creatinine at similar time points. At 48 ho urs, CNI-1493 significantly abrogated the increase in PVP compared with IRI alone. However, CNI-1493 did not alter the course of the acute renal failu re. Pulmonary histology demonstrated interstitial edema, alveolar hemorrhag e, and red blood cell sludging after renal IRI, which was partially attenua ted by CNI-1493. Conclusions. Increased PVP develops after isolated renal IRI, and macrophag e-derived products are mediators in this response. These findings have impl ications for understanding the mechanisms underlying respiratory dysfunctio n associated with acute renal failure.