Both acute lung injury and acute kidney injury (AKI) are frequent and serious problems in intensive care medicine. Therefore, the avoiding of any iatrogenic insult to these organs is of great importance. While an increasing body of evidence suggests that mechanical ventilation is capable of inducing lung and distant organ injury, the complex underlying molecular mechanisms remain insufficiently understood. In the previous issue of Critical Care, Vaschetto and colleagues reported the results of an experimental study designed to further explore pathways linking injurious ventilation with AKI. The authors demonstrated that scavenging of peroxynitrite or inhibiting poly(ADP-ribose) polymerase (PARP) afforded protection against AKI induced by double-hit lung injury. Although PARP inhibition or peroxynitrite detoxification or both may become viable candidates for a protective strategy in this setting, the implementation of a lung-protective ventilatory strategy remains the only clinical tool to mitigate the lung biotrauma and its systemic consequences.

1st Medical Department Charles University Medical School and Teaching Hospital alej Svobody 80 304 60 Plzen Czech Republic

Crit Care. 2010;14(2):R45. doi: 10.1186/cc8932. PubMed

See more in PubMed

Vaschetto R, Kuiper JW, Musters RJ, Eringa EC, Della Corte F, Murthy K, Groeneveld AJ, Plotz FB. Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway. Crit Care. 2010;14:R45. doi: 10.1186/cc8932. PubMed DOI PMC

Pannu N, Mehta RL. Mechanical ventilation and renal function: an area for concern? Am J Kidney Dis. 2002;39:616–624. doi: 10.1053/ajkd.2002.31419. PubMed DOI

Kuiper JW, Groeneveld AB, Slutsky AS, Plötz FB. Mechanical ventilation and acute renal failure. Crit Care Med. 2005;33:1408–1415. doi: 10.1097/01.CCM.0000165808.30416.EF. PubMed DOI

Slutsky AS, Tremblay LN. Multiple system organ failure. Is mechanical ventilation a contributing factor? Am J Respir Crit Care Med. 1998;157:1721–1725. PubMed

Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ. Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses. Intensive Care Med. 2004;30:1865–1872. doi: 10.1007/s00134-004-2363-9. PubMed DOI

Imai Y, Parodo J, Kajikawa O, de PM, Fischer S, Edwards V, Cutz E, Liu M, Keshavjee S, Martin TR, Marshall JC, Ranieri VM, Slutsky AS. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA. 2003;289:2104–2112. doi: 10.1001/jama.289.16.2104. PubMed DOI

Douillet CD, Robinson WP, Zarzaur BL, Lazarowski ER, Boucher RC, Rich PB. Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs. Am J Respir Cell Mol Biol. 2005;32:52–58. doi: 10.1165/rcmb.2004-0177OC. PubMed DOI

Koyner JL, Murray PT. Mechanical ventilation and the kidney. Blood Purif. 2010;29:52–68. doi: 10.1159/000259585. PubMed DOI PMC

Ricci Z, Ronco C. Pulmonary/renal interaction. Curr Opin Crit Care. 2010;16:13–18. doi: 10.1097/MCC.0b013e328334b13b. PubMed DOI

Barth E, Radermacher P, Szabó C. The world according to poly(ADP-ribose) polymerase (PARP)--update 2006. Intensive Care Med. 2006;32:1470–1474. doi: 10.1007/s00134-006-0336-x. PubMed DOI

Maier C, Scheuerle A, Hauser B, Schelzig H, Szabó C, Radermacher P, Kick J. The selective poly(ADP)ribose-polymerase 1 inhibitor INO1001 reduces spinal cord injury during porcine aortic cross-clamping-induced ischemia/reperfusion injury. Intensive Care Med. 2007;33:845–850. doi: 10.1007/s00134-007-0585-3. PubMed DOI

Gerö D, Szabó C. Poly(ADP-ribose) polymerase: a new therapeutic target? Curr Opin Anaesthesiol. 2008;21:111–121. doi: 10.1097/ACO.0b013e3282f63c15. PubMed DOI

Kim JH, Suk MH, Yoon DW, Kim HY, Jung KH, Kang EH, Lee SY, Lee SY, Suh IB, Shin C, Shim JJ, In KH, Yoo SH, Kang KH. Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury. Crit Care. 2008;12:R108. doi: 10.1186/cc6995. PubMed DOI PMC

Devalaraja-Narashimha K, Singaravelu K, Padanilam BJ. Poly(ADP-ribose) polymerase-mediated cell injury in acute renal failure. Pharmacol Res. 2005;52:44–59. doi: 10.1016/j.phrs.2005.02.022. PubMed DOI

Heemskerk S, Masereeuw R, Russel FG, Pickkers P. Selective iNOS inhibition for the treatment of sepsis-induced acute kidney injury. Nat Rev Nephrol. 2009;5:629–640. doi: 10.1038/nrneph.2009.155. PubMed DOI

Matejovic M, Krouzecky A, Martinkova V, Rokyta R Jr, Kralova H, Treska V, Radermacher P, Novak I. Selective inducible nitric oxide synthase inhibition during long-term hyperdynamic porcine bacteremia. Shock. 2004;21:458–465. doi: 10.1097/00024382-200405000-00010. PubMed DOI

Vaschetto R, Kuiper JW, Chiang SR, Haitsma JJ, Juco JW, Uhlig S, Plotz FB, Corte FD, Zhang H, Slutsky AS. Inhibition of poly(adenosine diphosphateribose) polymerase attenuates ventilator-induced lung injury. Anesthesiology. 2008;108:261–268. doi: 10.1097/01.anes.0000299434.86640.15. PubMed DOI PMC

Le Dorze M, Legrand M, Payen D, Ince C. The role of the microcirculation in acute kidney injury. Curr Opin Crit Care. 2009;15:503–508. doi: 10.1097/MCC.0b013e328332f6cf. PubMed DOI

Jang HR, Rabb H. The innnate immune response in ischemic acute kidney injury. Clin Immunol. 2009;130:41–50. doi: 10.1016/j.clim.2008.08.016. PubMed DOI PMC