Sepsis-associated Acute Kidney Injury Subphenotypes in Critically Ill Patients by Staging Trajectories
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Abstract
Background: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The current Kidney Disease: Improving Global Outcomes (KDIGO) criteria rely on maximal serum creatinine levels, which do not account for longitudinal changes. This study aimed to examine AKI staging trajectories and hypothesized that subphenotypes based on these trajectories are associated with different outcomes.
Methods: Two independent databases of patients in the intensive care unit (ICU) with AKI in Southeast Asia were analyzed. The SEA-AKI cohort served as the development cohort, while the KCMH cohort was used for validation. Group-based trajectory modelling identified subphenotypes of AKI staging in septic patients during the first seven days after ICU admission. Baseline characteristics, AKI staging, duration, recovery, and the occurrence and staging of acute kidney disease were compared between clusters. Associations between clusters and 28-day mortality, ICU and hospital mortality, and major adverse kidney events at day 28 (MAKE28) were evaluated.
Results: A total of 457 patients were included in the development cohort and 333 in the validation cohort. AKI occurred in 70.7% of the development cohort and 63.4% of the validation cohort. Three distinct clusters of AKI staging trajectories were identified in the development cohort: Cluster 1 (No AKI, 29.3%), Cluster 2 (early mild transient AKI, 50.9%), and Cluster 3 (early severe persistent AKI, 19.7%). Compared with the other clusters, an independent association was found between Cluster 3 and increased 28-day mortality. These findings were confirmed in the validation cohort.
Conclusions: AKI staging trajectories identified distinct subphenotypes associated with different outcomes. Further studies are needed to explore subphenotype-based interventions.
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