TY - JOUR
T1 - Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability
AU - Kramer, Andrew A.
AU - Postler, Gilbert
AU - Salhab, Khaled F.
AU - Mendez, Cynthia
AU - Carey, Larry C.
AU - Rabb, Hamid
N1 - Funding Information:
A.K. is supported by AT&T as the recipient of the Surgical Scholars Grant. H.R. is supported by an American Heart Association, FL, Grant-in Aid, Hermundslie Trust, and the Minneapolis Medical Research Foundation. The authors thank Ms. Jan Lovick for assistance in manuscript preparation. This work was presented in part at the American Society of Nephrology annual meeting, which was held on October 27, 1998 in Philadelphia. Publication of the color figure was assisted by educational grants from Merck and Co., Inc., and Astra Pharmaceuticals.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Acute renal failure
KW - Adult respiratory distress syndrome
KW - Cardiorespiratory failure
KW - Dialysis
KW - Macrophage
KW - Multiorgan failure
KW - Pulmonary vascular injury
KW - Remote organ injury
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U2 - 10.1046/j.1523-1755.1999.00460.x
DO - 10.1046/j.1523-1755.1999.00460.x
M3 - Article
C2 - 10354283
AN - SCOPUS:0032991434
SN - 0085-2538
VL - 55
SP - 2362
EP - 2367
JO - Kidney international
JF - Kidney international
IS - 6
ER -