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Three blood metabolites flag sepsis-associated kidney injury early

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Mouse kidney multi-omics plus a 56-patient serum cohort produced an IC3 model (inosine, creatine, 3-hydroxybutyric acid) that early-identified sepsis-associated AKI with AUC 0.90.

Source

Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury

Huang P, Liu Y, Li Y, et al. · BMC medicine · 2025

doi.org/10.1186/s12916-025-03920-7Read the full paper ↗37 citationscc by

Study at a glance

Design
Other — Mouse LPS SA-AKI multi-omics discovery plus targeted serum metabolomics validation in patients
N
N=56 · Clinical validation: 28 SA-AKI vs 28 sepsis without SA-AKI; mouse discovery separate
Population
Patients with sepsis with or without SA-AKI (mouse model for discovery)
Outcome
Early SA-AKI identification by metabolite panel (IC3 AUC)

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Authors ran untargeted renal proteomics/metabolomics in LPS-induced SA-AKI mouse models with real-time GFR monitoring, built multi-omics correlation networks, then validated core metabolites with targeted serum metabolomics in 56 patients (28 SA-AKI vs 28 sepsis without the SA-AKI label used in the model).

What they found

Core metabolites including inosine, creatine, and 3-hydroxybutyric acid supported an IC3 logistic model for early SA-AKI identification (AUC 0.90). Background clinical framing notes that roughly one-third of ICU sepsis patients develop SA-AKI.

The limits

What it doesn't show

AUC 0.90 comes from a modest 56-patient cohort and needs external prospective validation before routine use. Mouse LPS models are not identical to human polymicrobial sepsis. The panel is a diagnostic aid hypothesis, not a replacement for creatinine/urine-output criteria or a treatment.

Key terms

SA-AKI
Sepsis-associated acute kidney injury.
IC3 model
Diagnostic model using inosine, creatine, and 3-hydroxybutyric acid.
Multi-omics
Here, integrated renal metabolomics and proteomics correlated with kidney function.
GFR monitoring
Real-time glomerular filtration rate measurement used in the mouse experiments.
LPS-induced SA-AKI
Lipopolysaccharide mouse model of sepsis-associated kidney injury.

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IC3 uses which metabolite trio?

Common questions

What is IC3?

A diagnostic model using inosine, creatine, and 3-hydroxybutyric acid to early-identify SA-AKI.

What performance did IC3 report?

AUC = 0.90 in the 56-patient serum cohort.

How common is SA-AKI in ICU sepsis (per authors’ framing)?

About one-third of ICU sepsis patients develop SA-AKI.

What preclinical work preceded the human model?

Untargeted renal proteomics/metabolomics in LPS-induced SA-AKI mice with GFR monitoring.

Ready for bedside replacement of AKI criteria?

Not yet — sample size is small and external validation is still required.

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