Risk Classification and Subphenotyping of Acute Kidney Injury: Concepts and Methodologies

Acute kidney injury (AKI) is a complex syndrome with a paucity of therapeutic development. One aspect that could explain the lack of implementation science in the AKI field is the vast heterogeneity of the AKI syndrome, which hinders precise therapeutic applications for specific AKI subpopulations. In this context, there is a consensual focus of the scientific community toward the development and validation of tools to better subphenotype AKI and therefore facilitate precision medicine approaches. The subphenotyping of AKI requires the use of specific methodologies suitable for interrogation of multimodal data inputs from different sources such as electronic health records, organ support devices, and/or biospecimens and tissues. Over the past years, the surge of artificial intelligence applied to health care has yielded novel machine learning methodologies for data acquisition, harmonization, and interrogation that can assist with subphenotyping of AKI. However, one should recognize that although risk classification and subphenotyping of AKI is critically important, testing their potential applications is even more important to promote implementation science. For example, risk-classification should support actionable interventions that could ameliorate or prevent the occurrence of the outcome being predicted. Furthermore, subphenotyping could be applied to predict therapeutic responses to support enrichment and adaptive platforms for pragmatic clinical trials.