in this issue of critical care , zwiers and colleagues   describe the incidence of acute kidney injury ( aki ) in neonates on extracorporeal membrane oxygenation ( ecmo ) based on a 12-year cohort study from sophia children s hospital pediatric intensive care unit in rotterdam , the netherlands
. of major interest , this study is looking at patients during an era when continuous renal replacement therapy ( crrt ) was not systematically used , giving a clearer perspective on the natural kinetics of renal function , estimated by serum creatinine ( scr ) , during ecmo course .
interestingly , the worst renal function occurred early during the ecmo run , within the first 2 days , and with a 2- to 4-day delay until renal function improvement could be observed .
this suggests that aki is an early event in newborns requiring ecmo support . establishing the  natural history of renal function in patients with multiple organ dysfunction syndrome ( mods ) gives us the expected time period during which one may 
, it would be valuable to know to what extent improving renal function during ecmo course really is associated with better outcome .
better characterization of mods timing in the course of heterogeneous life - threatening diseases is central .
international integrated database for the evaluation of severe sepsis and drotrecogin alfa ( activated ) therapy database analysis , regrouping 4,459 patients with sepsis , showed that worsening organ failures  particularly , cardiovascular , respiratory , renal , and hematologic failure  was the cause of death in patients with sepsis .
interestingly , it showed that aggravating renal sequential organ failure assessment score was a late event close to death .
one can hypothesize that bi - modal impairment in renal function should result in a more severe outcome . in children and neonates ,
similar data were published . aggravating pediatric logistic organ dysfunction score within the first 4 days
was associated with a 50% mortality . however , in newborns , renal dysfunction does not seem to have a major impact on mortality .
in the present study , the authors showed that severity of renal failure was strongly associated with mortality ; the odds ratio of mortality for acute kidney failure ( identified as an scr of greater than 300% of normal value ) was 12.7 .
this suggests that , although knowing aki natural course during ecmo may give arguments for delaying crrt , there is clearly a cutoff value at which aki severity directly impacts mortality .
it is not the purpose of this commentary to discuss the ideal timing of crrt during ecmo , because many questions remain to be debated , but this study confirms that aki is a major outcome determinant in the course of ecmo . if not an unresolved dilemma , aki in the course of mods remains a circular reference : aki in patients requiring ecmo therapy is triggered by initial systemic insults , already present at the time of ecmo initiation , and aggravated by reperfusion injury and ecmo circuit - induced inflammation .
the close interplay between the cause and severity of the disease , supportive therapies , and host response is influencing the development of aki and mods .
identifying as well as determining the relative importance of extrinsic factors a ggravating mods / aki during ecmo therapy is central . besides technologic advances in ecmo circuit biocompatibility improvement
reperfusion as well as function , identifying deleterious therapeutic interventions , and improving standard therapies , such as antimicrobial chemotherapy .
recently , it was shown in an autopsy series of patients dying of septic shock that renal dysfunction was due mostly to focal renal tubular injury through apoptosis and not autophagy .
that study clearly suggested that renal dysfunction found in patients dying of sepsis - induced mods is reversible .
ecmo is certainly among the greatest recent advances , making a surgical theater technique widely available in the critical care setting for clinical conditions far away from the original cardiovascular indications .
however , a lot remains to be done in order to identify proper indications , optimize all organ support , reduce complications , and better characterize pathophysiologic and cellular mechanisms of organ dysfunctions in children under ecmo .
aki : acute kidney injury ; crrt : continuous renal replacement therapy ; ecmo : extracorporeal membrane oxygenation ; mods : multiple organ dysfunction syndrome ; scr : serum creatinine .
 whether the egg or the chicken came first remains debated , although the debate is not critical for those who love eating omelets . 
 at least , it is well accepted that one needs to break eggs to fry an omelet . in some ways , there are similarities with acute kidney injury . 
 a lot of debate arises from whether acute kidney injury is a complication of various insults and therapies or an expected continuum of the organ failure process . 
 indeed , it is well accepted that acute renal failure is associated with increased mortality in severely ill children and infants . 
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