Construction and diagnostic efficacy assessment of the urinary exosomal <scp>miRNA</scp> ‐ <scp>mRNA</scp> network in children with <scp>IgA</scp> vasculitis nephritis

This study aimed to comprehensively evaluate the diagnostic potential of urinary exosomal microRNA (miRNA) in IgA vasculitis (IgAV) kidney injury by meticulously comparing the miRNA expression profiles in urine exosomes between children diagnosed with IgAV and those with IgA vasculitis nephritis (IgAVN). Urine samples were obtained from children with IgAV who were treated at our hospital from October 2022 to October 2023. These samples were then categorized into the IgAV group and the IgAVN group. High-throughput sequencing and bioinformatics analysis techniques were employed to conduct a thorough analysis of the differentially expressed miRNAs between the two groups. Additionally, the correlation between urinary exosomal miRNA and clinical parameters was evaluated. A total of 57 urinary exosomal miRNAs exhibited differential expression between the IgAV and IgAVN groups. Specifically, in the IgAVN group, 42 miRNAs were upregulated, while 15 were downregulated. Lasso regression analysis and ROC analysis identified five candidate urinary exosomal miRNAs with high diagnostic accuracy. A prediction of 95 target genes related to the candidate miRNAs led to the construction of an exosomal miRNA-mRNA regulatory network consisting of four key miRNAs and ten hub genes. Gene function and metabolic pathway analyses indicated that these ten hub genes were predominantly enriched in pro-fibrotic and inflammatory pathways. The analysis incorporating clinical parameters demonstrated a significant correlation between hsa-miR-383-5p and urinary protein levels. This research identified exosomal miRNAs and mRNAs with differential expression patterns associated with IgAVN and constructed the corresponding exosomal miRNA-mRNA network. It was determined that hsa-miR-3065-5p, hsa-miR-383-5p, hsa-miR-25-3p, and hsa-miR-450b-5p might mediate the pathogenesis of IgAVN by targeting pro-fibrotic and inflammatory pathways. Among them, exosomal hsa-miR-383-5p is highly likely to serve as a novel non-invasive biomarker for assessing the disease status of IgAVN, thereby offering new perspectives on the non-invasive diagnosis and treatment of IgAVN.