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

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 H 2 O 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.