Mallory PP, Selewski DT, Askenazi DJ, et al. - In this retrospective observational cohort study of 424 patients < 18 years of age supported with extracorporeal membrane oxygenation (ECMO) for ≥ 24 hours for a respiratory indication, the association between acute kidney injury (AKI), fluid overload (FO), and mortality was investigated. This study was performed at six tertiary care children’s hospital intensive care units from January 1, 2007, to December 31, 2011. The multivariate analysis suggests no correlation of FO level at ECMO initiation with hospital mortality, whereas there was an association of peak FO level during ECMO with hospital mortality. Nearly 1.2 times higher odds of hospital mortality were observed for every 10% increase in peak FO during ECMO. Every 10% increase in peak FO during ECMO led to a significant relative change in the duration of ECMO hours by a factor of 1.08 and a significant relative change in the duration of mechanical ventilation hours by a factor of 1.13 in-hospital survivors. These findings suggest and emphasize considering the association of AKI and FO with increased mortality as targets for medical interventions including judicious fluid management, diuretic use, and renal replacement therapy.