Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study

BMC Nephrology

Research Article

AB Johan Groeneveld¹  Serge Jothy²  Jan Willem Kuiper³  Mark PV Begieneman⁴  Lonneke Smeding⁵  Frans B Plötz⁶  Jack J Haitsma⁷  Rosanna Vaschetto⁸ 

[1] Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands;Department of Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada;Department of Paediatric Intensive Care, Erasmus MC – Sophia Children’s Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands;The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada;Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands;Department of Pediatrics and Pediatric Intensive Care, VU Medical Center, Amsterdam. Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;Department of Pediatrics, Tergooiziekenhuizen, Blaricum, The Netherlands;The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada;The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada;Departments of Anesthesiology and Critical Care Medicine, Università del Piemonte Orientale “A. Avogadro” Alessandria-Novara-Vercelli, Viale Teresa Michel, 11, Alessandria, Italy;Department of Clinical and Experimental Medicine, Università del Piemonte Orientale “A. Avogadro” Alessandria-Novara-Vercelli, Viale Teresa Michel, 11, Alessandria, Italy;

关键词: Acute kidney injury;    Acute respiratory distress syndrome;    Apoptosis;    Mechanical ventilation;    Sepsis;   

DOI  :  10.1186/1471-2369-15-126

 received in 2013-12-19, accepted in 2014-07-08,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIntratracheal aspiration and sepsis are leading causes of acute lung injury that frequently necessitate mechanical ventilation (MV), which may aggravate lung injury thereby potentially increasing the risk of acute kidney injury (AKI). We compared the effects of ventilation strategies and underlying conditions on the development of AKI.MethodsSpraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause more lung injury after acid instillation than in sepsis. Rats were ventilated for 4 hrs and kidney function and plasma mediator levels were measured. Kidney injury was assessed by microscopy; apoptosis was quantified by TUNEL staining.ResultsDuring sepsis, but not after acid instillation, MV with HVT caused more renal apoptosis than MV with LVT. Increased plasma active plasminogen activator inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased apoptosis after HVT ventilation during sepsis was associated with a 40% decrease in creatinine clearance.ConclusionsAKI is more likely to develop after MV induced lung injury during an indirect (as in sepsis) than after a direct (as after intra-tracheal instillation) insult to the lungs, since it induces kidney apoptosis during sepsis but not after acid instillation, opposite to the lung injury it caused. Our findings thus suggest using protective ventilatory strategies in human sepsis, even in the absence of overt lung injury, to protect the kidney.

【 授权许可】

CC BY   
© Kuiper et al.; licensee BioMed Central Ltd. 2014