FGA Serves as a Potential Diagnostic Marker and Therapeutic Target for Elderly Acute Kidney Injury.

Abstract

To identify potential biomarkers and explore the underlying mechanisms of elderly acute kidney injury (e-AKI), we performed integrative plasma proteomics analysis on samples from 20 e-AKI patients and 20 age-matched non-AKI controls. Differential expression gene analysis, GSEA, WGCNA, random forest, and LASSO models were employed to identify hub genes, coupled with immune cell infiltration and clinicopathological correlation analyses. A renal ischemia-reperfusion injury mouse model validated key genes at protein and mRNA levels, while in vitro experiments explored the pathway involvement. We identified 229 e-AKI-associated genes enriched in immune, inflammatory, and coagulation pathways. Machine learning combined with the Nephroseq database yielded three hub genes; in vivo and in vitro experiments confirmed fibrinogen alpha chain (FGA) as the most relevant gene, which may regulate e-AKI progression via the cAMP/PKA/CREB pathway. Collectively, FGA holds promise as a diagnostic biomarker and therapeutic target for e-AKI, laying the theoretical foundation for its mechanistic research.