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

BMC Nephrology

Frans B Plötz²  Rosanna Vaschetto³  Serge Jothy⁴  Mark PV Begieneman⁵  Lonneke Smeding⁶  Jack J Haitsma⁷  AB Johan Groeneveld¹  Jan Willem Kuiper⁷ 

[1] Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands;Department of Pediatrics, Tergooiziekenhuizen, Blaricum, The Netherlands;Department of Clinical and Experimental Medicine, Università del Piemonte Orientale “A. Avogadro” Alessandria-Novara-Vercelli, Viale Teresa Michel, 11, Alessandria, Italy;Department of Laboratory Medicine, St. Michael’s Hospital, 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;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

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

Others  :  1082647
DOI  :  10.1186/1471-2369-15-126

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

【 摘 要 】

Background

Intratracheal 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.

Methods

Spraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LV_T) and 5 cm H₂O positive end-expiratory pressure (PEEP) or a high tidal volume (HV_T) 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.

Results

During sepsis, but not after acid instillation, MV with HV_T caused more renal apoptosis than MV with LV_T. Increased plasma active plasminogen activator inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased apoptosis after HV_T ventilation during sepsis was associated with a 40% decrease in creatinine clearance.

Conclusions

AKI 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】

   
2014 Kuiper et al.; licensee BioMed Central Ltd.

【 图 表 】

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