Identification of core genes in acute kidney injury: evidence from multi-omics human transcriptomic data and models.

BACKGROUND

Acute kidney injury (AKI) affects up to 23.2% of hospitalized patients, but its complex pathophysiology hinders diagnosis and treatment. Bioinformatics-driven identification of core genes from large-scale omics data offers a promising approach for uncovering diagnostic and therapeutic targets. This study aims to integrate multi-omics data with experimental validation to identify core genes involved in AKI and explore their mechanisms.

METHODS

We analyzed renal transcriptomic data from 67 AKI patients and 20 controls, integrating differential expression, weighted gene co-expression network analysis (WGCNA), and clinical correlations to identify key genes. A nomogram model was used to assess diagnostic performance, and immune microenvironment characteristics were analyzed using CIBERSORT. AKI was induced in mice by ischemia-reperfusion and cisplatin, with gene expression validated by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. expression and function were further examined in proximal tubules (PT) using human single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics.

RESULTS

Three core genes, epidermal growth factor (), vascular cell adhesion molecule 1 (), and , were identified, showing significant associations with AKI phenotypes and clinical renal parameters. Combined, these genes provided a robust diagnostic model for AKI. CIBERSORT associated with monocytes, with monocytes and M2 macrophages, and with monocytes and T cells. Both mouse models showed downregulation of and , and upregulation of , consistent with human data. Single-nucleus RNA sequencing revealed that was highly expressed in healthy PT but downregulated in severely injured PT. Low expression correlated with suppressed mitochondrial functions and activated immune responses. Spatial transcriptomics confirmed that regions of high expression co-localized with areas of oxidative phosphorylation activity in PT.

CONCLUSIONS

This study highlights three core genes of AKI, especially , which is related to mitochondrial metabolism and immune balance in PT during AKI, offering potential diagnostic and therapeutic targets.