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Updated: Apr 18, 2026

Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis
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Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis

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Urine proteomic profiling at admission reveals complement biomarkers linked to alcohol-associated liver disease

Luan Prado, Ryan Musich, Moyinoluwa Taiwo

    Biorxiv : the Preprint Server for Biology
    |April 17, 2026
    PubMed

    Insights

    Urinary complement proteins may serve as biomarkers for alcohol-associated liver disease (ALD) and alcohol-associated hepatitis (AH), offering insights into liver-kidney crosstalk. These findings could aid in distinguishing AH from alcohol cirrhosis (AC).

    Area of Science:

    • Immunology
    • Nephrology
    • Hepatology

    Background:

    • Circulating complement is linked to alcohol-associated hepatitis (AH) and can differentiate it from alcohol cirrhosis (AC).
    • Complement activation contributes to kidney injury in alcohol-associated liver disease (ALD), but liver-kidney crosstalk mechanisms remain unclear.
    • This study investigates urinary complement as potential biomarkers for ALD and liver-kidney crosstalk.

    Purpose of the Study:

    • To test the hypothesis that urinary complement proteins can serve as biomarkers for ALD.
    • To gain insights into the mechanisms of liver-kidney crosstalk in ALD pathogenesis.
    • To evaluate the potential of urinary complement to distinguish between severe AH (sAH) and AC.

    Main Methods:

    • Collected plasma and urine samples from patients with sAH, healthy controls (HC), heavy drinkers (HD), and patients with AC.
    • Performed unbiased proteomics analysis on urine samples.
    • Assessed plasma complement using multiplex/ELISA assays and tracked 30- and 90-day mortality in sAH patients.

    Main Results:

    • All three complement pathways were altered in plasma and urine of sAH and AC patients compared to HC and HD.
    • Urinary complement components correlated with mortality in sAH patients.
    • A panel of four urinary complement proteins distinguished sAH from AC with an AUC of 0.78, comparable to MELD (AUC 0.65).
    • No correlation was found between plasma and urinary complement levels.

    Conclusions:

    • Urinary proteomic analysis identified complement protein signatures associated with sAH and AC.
    • Urinary complement shows potential as biomarkers for ALD.
    • Findings provide insights into liver-kidney crosstalk mechanisms in ALD pathogenesis.
    Abstract

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