Clustering analysis of multi-site electronic health records reveals distinct subphenotypes in stage-1 acute kidney injury
Abstract Background Acute Kidney Injury (AKI) can adversely affect multiple organ systems, including the heart, brain, and immune system. Stage 1 AKI (AKI-1), although mild in clinical presentation, constitutes a substantial subset of AKI patients with heterogeneous outcomes, warranting further inve...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00993-6 |
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| Summary: | Abstract Background Acute Kidney Injury (AKI) can adversely affect multiple organ systems, including the heart, brain, and immune system. Stage 1 AKI (AKI-1), although mild in clinical presentation, constitutes a substantial subset of AKI patients with heterogeneous outcomes, warranting further investigation into its subphenotypes. Methods We performed clustering analysis on seven-day serum creatinine (SCr) trajectories preceding AKI-1 onset in 53,565 AKI-1 patients (aged 18–89 years; 55.57% male) across eight academic hospitals. Each AKI-1 patient was matched to a non-AKI counterpart to evaluate how different AKI-1 subphenotypes influence clinical indicators and outcomes. Results Three distinct AKI-1 subphenotypes are identified. Patients in Subphenotype C (n = 5,378; 10.0%) exhibit a higher proportion of abnormal values across clinical indicators compared to those in Subphenotypes A (n = 27,049; 50.5%) and B (n = 21,138; 39.5%). Subphenotype C is associated with significantly higher odds ratios (ORs) for in-hospital, 30-day, and one-year all-cause mortality relative to Subphenotypes A and B. Conversely, Subphenotype B exhibits a higher susceptibility to developing chronic kidney disease (CKD) within one year after discharge following AKI-1, compared to both Subphenotypes A and C, after adjustment for baseline SCr levels. All AKI-1 subphenotypes are associated with significantly elevated risks of all-cause mortality and the need for dialysis or renal replacement therapy (RRT) compared to their respective non-AKI counterparts. Conclusions This study reveals substantial heterogeneity in clinical indicators and outcomes within AKI-1. Future research focusing on these subphenotypes may pave the way for more personalized and targeted interventions for patients with AKI-1. |
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| ISSN: | 2730-664X |