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Article Abstract

Objective: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease, with chronic inflammation driving its progression. This study aimed to identify immune-related diagnostic biomarkers for DKD and explore their association with immune cell infiltration.

Methods: Three glomerular transcriptomic datasets (53 DKD, 36 controls) were analyzed via batch-corrected differential expression analysis to screen immune-related differentially expressed genes (DEGs). Machine learning algorithms (least absolute shrinkage and selection operator, support vector machine - recursive feature elimination) prioritized biomarkers, validated by RT-PCR in db/db mice. Immune infiltration was assessed via CIBERSORT and EPIC.

Results: Thirteen immune DEGs were identified, enriched in cytokine signaling and leukocyte chemotaxis. Three biomarkers (albumin (ALB), AP - 1 transcription factor subunit (FOS), and S100 calcium binding protein A9) showed strong correlations with T cell, natural killer cell, and macrophage infiltration, validated by RT-PCR ( < 0.001). Protein-protein interactionnetwork analysis identified ALB and FOS as hub genes (ROC Area Under the Curve: 0.803, 0.795), linking immune dysregulation to glomerular injury.

Conclusion: ALB and FOS serve as novel immunogenetic biomarkers for DKD, highlighting chronic inflammation as a key driver. This framework supports precision immunomodulation, though clinical validation in larger cohorts is needed.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247103PMC
http://dx.doi.org/10.1080/0886022X.2025.2525467DOI Listing

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