Plasma proteomics defines two reproducible subphenotypes of sepsis-associated acute kidney injury with distinct outcomes.

Summary

Using ensemble clustering across three independent patient groups, the study identified two reproducible plasma-proteomic subphenotypes of sepsis-associated acute kidney injury. The inflammatory subtype had higher mortality and morbidity, while a seven-protein panel reproduced the classification in separate cohorts; exploratory randomized-trial data suggested benefit from ilofotase alfa in the inflammatory subtype.

Key Findings

• Sepsis-associated acute kidney injury contained two reproducible plasma-proteomic subphenotypes across three independent patient groups.
• The inflammatory subphenotype showed broad activation of inflammation, metabolism, and oxidative stress and was associated with higher mortality, more complications, and fewer ICU-free days.
• A seven-protein panel accurately reproduced the subphenotypes in separate cohorts, and exploratory randomized-trial data suggested benefit from ilofotase alfa in the inflammatory subtype.

Clinical Implications

A seven-protein assay could eventually support risk stratification and selection of patients for targeted therapies such as ilofotase alfa. The findings are not yet sufficient for routine clinical use and require prospective validation with analytically standardized testing and treatment-stratified trials.

Limitations

• The treatment-response evidence for ilofotase alfa is exploratory and does not establish efficacy for clinical practice.
• The abstract does not provide the cohort sizes, assay details, or complete performance characteristics needed to assess implementation of the seven-protein test.

Future Directions

Prospective multicenter validation should confirm the subphenotypes using standardized assays, determine whether classification changes over time, and test biomarker-guided treatment allocation in adequately powered randomized trials.