Acute Kidney Injury (AKI) cannot be viewed as a mere complication in critically ill patients who require extracorporeal membrane oxygenation (ECMO). Rather, it is being increasingly recognized as an important determinant that may alter the course of illness, with long term sequelae in patients requiring ECMO and portending a worse prognosis. The underlying mechanisms for AKI among patients requiring ECMO are complex and include hemodynamic instability, an inflammatory response, coagulation and platelet abnormalities, and immune-mediated injury that arise from the primary underlying disease, premorbid conditions, and the ECMO circuit^1,2 (Figure 1). More than half of the patients who need ECMO therapy need renal replacement therapy and the mortality reported in this cohort is high. Patients needing venoarterial (VA) ECMO tend to have a higher mortality associated with AKI when compared to those needing venovenous (VV) ECMO.^3,4 Similar findings have been established in patients with other mechanical cardiac support devices, such as left ventricular assist device support after cardiogenic shock, where approximately one-third of patients require concurrent renal replacement therapy and have a significantly greater odds of in-hospital and overall mortality compared to those not needing it.⁵ Importantly, the development of AKI during ECMO signals a trajectory toward worse outcomes, underscoring the need for early identification, risk stratification, and management.