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Background: Acute kidney injury (AKI) is a multifaceted disease characterized by diverse clinical presentations and mechanisms. Advances in artificial intelligence have propelled the identification of AKI subphenotypes, enhancing our capacity to customize treatments and predict disease trajectories., Methods: We conducted a systematic review of the literature from 2017 to 2022, focusing on studies that utilized machine learning techniques to identify AKI subphenotypes in adult patients. Data were extracted regarding patient demographics, clustering methodologies, discriminators, and validation efforts from selected studies., Results: The review highlights significant variability in subphenotype identification across different populations. All studies utilized clinical data such as comorbidities and laboratory variables to group patients. Two studies incorporated biomarkers of endothelial activation and inflammation into the clinical data to identify subphenotypes. The primary discriminators were comorbidities and laboratory trajectories. The association of AKI subphenotypes with mortality, renal recovery and treatment response was heterogeneous across studies. The use of diverse clustering techniques contributed to variability, complicating the application of findings across different patient populations., Conclusions: Identifying AKI subphenotypes enables clinicians to better understand and manage individual patient trajectories. Future research should focus on validating these phenotypes in larger, more diverse cohorts to enhance their clinical applicability and support personalized medicine in AKI management., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)