title: Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study.
abstract: 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 (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.
  
  
  RESULTS
  During 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.
  
  
  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.
authors: Department of Paediatric Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr, Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. j.kuiper@erasmusmc.nl.
authors: Jan Willem
authors: JW
authors: Kuiper
authors: A B Johan
authors: AB
authors: Groeneveld
authors: Jack J
authors: JJ
authors: Haitsma
authors: Lonneke
authors: L
authors: Smeding
authors: Mark P V
authors: MP
authors: Begieneman
authors: Serge
authors: S
authors: Jothy
authors: Rosanna
authors: R
authors: Vaschetto
authors: Frans B
authors: FB
authors: Plötz
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity*; D007442:Intubation, Intratracheal / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D018805:Sepsis / Q000139:chemically induced / Q000473:pathology*
chemical_list: D006851:Hydrochloric Acid