Acute kidney injury (AKI) is a threatening medical condition associated with poor outcomes at different settings. The development of standardized diagnostic criteria and new biomarkers addressed significant clinical impacts of AKI and the need for an early AKI detection, respectively. There have been some breakthroughs in understanding the pathogenesis of AKI through basic research; however, treatments against AKI aside from renal replacement therapy (RRT) have not shown adequate successful results. Biomarkers that could identify good responders to certain treatment are expected to facilitate translation of basic research findings. Most patients with severe AKI treated with RRT died due to multiple-organ failure, not renal dysfunction. Hence, it is essential to identify other organ dysfunctions induced by AKI as organ crosstalk. Also, a multidisciplinary approach of critical care nephrology is needed to evaluate a complex organ crosstalk in AKI. For disruptive innovation for AKI, we further explore these new aspects of AKI, which previously were considered outside the scope of nephrology.