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Critical care

Three blood metabolites flag sepsis-associated kidney injury early

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

Open access · cc by · source: Europe PMC

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.

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.

Key findings

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.

Methodology

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).

Limitations

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.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • QualifiesSepsisconcept

    Blood leukocyte transcriptomes split ICU pneumonia sepsis into SRS1 vs SRS2 with different early mortality.

    In prospective UK ICU adults with community-acquired pneumonia sepsis, unsupervised transcriptomics defined SRS1 (~41%) as an immunosuppressed state with higher 14-day mortality than SRS2 (discovery HR 2.4; validation HR 2.8), classifiable with a seven-gene set.

    Scope note — different organ focus — early SA-AKI metabolites, not whole-blood SRS classes

    Limits the claim's scope: a different population, assay, or outcome.

  • SupportsSepsisconcept

    A three-metabolite serum panel can flag sepsis-associated AKI early in a small cohort.

    After mouse kidney multi-omics discovery, a 56-patient serum cohort supported an IC3 model (inosine, creatine, 3-hydroxybutyric acid) for early SA-AKI identification (AUC 0.90).

    Evidence for the claim as stated.

  • SupportsSepsisconcept

    IC3 targets early recognition of SA-AKI; SRS targets host-response prognosis. Shared sepsis context does not make kidney metabolites interchangeable with blood immune subtypes.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    SupportsSepsis

    IC3 targets early recognition of SA-AKI; SRS targets host-response prognosis. Shared sepsis context does not make kidney metabolites interchangeable with blood immune subtypes.

    Also on this tension

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Same topic cluster — not a recommendation engine.