Background: Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS. Objectives: The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF. Methods: We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs. Results: Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-α increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions. Conclusions: We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.

Star RA: Treatment of acute renal failure. Kidney Int 1998;54:1817–1831.
Chertow GM, Levy EM, Hammermeister KE, Grover F, et al: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998;104:343–348.
Chertow GM, Christiansen CL, Cleary PD, Munro C, Lazarus JM: Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med 1995;155:1505–1511.
Piastra M, Ruggiero A, Langer A, Caresta E, Chiaretti A, Pulitano S, Polidori G, Riccardi R: Pulmonary hemorrhage complicating a typical hemolytic-uremic syndrome. Respiration 2004;71:537–541.
Kramer AA, Postler G, Salhab KF, Mendez C, Carey LC, Rabb H: Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Kidney Int 1999;55:2362–2367.
Rabb H, Wang Z, Nemoto T, Hotchkiss J, Yokota N, Soleimani M: Acute renal failure leads to dysregulation of lung salt and water channels. Kidney Int 2003;63:600–606.
Deng J, Hu X, Yuen PS, Star RA: α-Melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion. Am J Respir Crit Care Med 2004;169:749–756.
Ware MB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000;342:1334–1349.
Luce JM: Acute lung injury and the acute respiratory distress syndrome. Crit Care Med 1998;26:369–376.
Bhatia M, Moochhala S: Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 2004;202:145–156.
Cohen J: The immunopathogenesis of sepsis. Nature 2002;420:885–891.
Puneet P, Moochhala S, Bhatia M: Chemokines in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 2005;288:L3–L15.
Hack CE, Hart M, van Schijndel RJ, Eerenberg AJ, Nuijens JH, Thijs LG, Aarden LA: Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun 1992;60:2835–2842.
Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger HG: The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut 1997;41:832–840.
Shokuhi S, Bhatia M, Christmas S, Sutton R, Neoptolemos JP, Slavin J: Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis. Br J Surg 2002;89:566–572.
Borkan SC, Gullans SR: Molecular chaperones in the kidney. Annu Rev Physiol 2000;64:503–527.
Beck FX, Neuhofer W, Muller E: Molecular chaperones in the kidney distribution, putative roles, and regulation. Am J Physiol 2000;279:F203–F215.
Frydman J: Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu Rev Biochem 2001;70:603–647.
Barazi HO, Zhou L, Templeton NS, Krutzsch HC, Roberts DD: Identification of heat shock protein 60 as a molecular mediator of α3β1 integrin activation. Cancer Res 2002;62:1541–1548.
Kurucz I, Morva A, Vaag A, Eriksson KF, Huang X, Groop L, Koranyi L: Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes 2002;51:1102–1109.
Villar J, Ribeiro SP, Mullen JB, Kuliszewski M, Post M, Slutsky AS: Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model. Crit Care Med 1994;22:914–921.
Javadpour M, Kelly CJ, Chen G, Bouchier-Hayes DJ: Herbimycin-A attenuates ischemia-reperfusion induced pulmonary neutrophil infiltration. Eur J Vasc Endovasc Surg 1998;16:377–382.
Koh Y, Lim CM, Kim MJ, Shim TS, Lee SD, Kim WS, Kim DS, Kim WD: Heat shock response decreases endotoxin-induced acute lung injury in rats. Respirology 1999;4:325–330.
Deshpande GG, Heidemann SM, Sarnaik AP: Heat stress is associated with decreased lactic acidemia in rat sepsis. Crit Care 2000;4:45–49.
Weiss YG, Bouwman A, Gehan B, Schears G, Raj N, Deutschman CS: Cecal ligation and double puncture impairs heat shock protein 70 (HSP-70) expression in the lungs of rats. Shock 2000;13:19–23.
Weiss YG, Maloyan A, Tazelaar J, Raj N, Deutschman CS: Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome. J Clin Invest 2002;110:801–806.
Dallal MM, Chang SW: Evans blue dye in the assessment of permeability-surface are product in perfused rat lungs. J Appl Physiol 1994;77:1030–1035.
Weiss YG, Tazelaar J, Gehan BA, Bouwman A, Christofidou-Solomidou M, Yu QC, Raj N, Deutschman CS: Adenoviral vector transfection into the pulmonary epithelium after cecal ligation and puncture in rats. Anesthesiology 2001;95:974–982.
Aytacoglu BN, Calikoglu M, Tamer L, Coskun B, Sucu N, Kose N, Aktas S, Dikmengil M: Alcohol-induced lung damage and increased oxidative stress. Respiration 2006;73:100–104.
Norman JG, Fink GW, Franz MG: Acute pancreatitis induces intrapancreatic tumor necrosis factor gene expression. Arch Surg 1995;130:966–970.
Vanderbilt JN, Mager EM, Allen L, Sawa T, Wiener-Kronish J, Gonzalez R, Dobbs LG: CXC chemokines and their receptors are expressed in type II cells and upregulated following lung injury. Am J Respir Cell Mol Biol 2003;29:661–668.
Belperio JA, Keane MP, Burdick MD, Londhe V, Xue YY, Li K, Phillips RJ, Strieter RM: Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest 2002;110:1703–1716.
Bhatia M, Brady M, Zagorski J, Christmas SE, Campbell F, Neoptolemos JP, Slavin J: Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury. Gut 2000;47:838–844.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.