Definitions, phenotypes, and subphenotypes in acute kidney injury—Moving towards precision medicine

The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding individualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology. Molecular signatures to identify subphenotypes are being recognised, as specific biomarkers reveal activated pathways. Assessment of individual clinical risk needs wider dissemination to allow identification of patients at high risk of AKI. New and more timely markers for glomerular filtration rate (GFR) are available. However, AKI diagnosis and classification should not be limited to GFR, but include tubular function and damage. Combining damage and stress biomarkers with functional markers enhances risk prediction, and identifies a population enriched for clinical trials targeting AKI. We review novel developments and aim to encourage implementation of these new techniques into clinical practice as a strategy for individualizing AKI treatment akin to a precision medicine‐based approach. Summary at a glance Current definitions of AKI are focused on the syndrome of AKI, a complex entity with many causes. Only supportive therapy is available as treatment of this syndrome. We suggest that reclassifying AKI according to causal phenotype and mechanism‐based subphenotypes defined by biomarkers is needed to provide a strategy for individualizing AKI diseases.