Abstract: Objective: This study aims to analyze the changes in plasma metabolites of pediatric patients with IgA nephropathy (IgAN) using non⁃targeted metabolomics, to identify potential non⁃invasive diagnostic biomarkers and provide a basis for early diagnosis of IgAN. Methodology: Plasma samples from IgAN pediatric patients hospitalized at Nanjing Children􀆳s Hospital from January to December 2024 were collected as the case group, and samples from healthy individuals undergoing physical examinations as the control group. Metabolomics analysis was performed using liquid chromatography⁃tandem mass spectrometry (LC⁃MS/MS). Differential metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS⁃DA), and metabolic pathway enrichment analysis was conducted with the KEGG database. Potential diagnostic biomarkers were identified via receiver operating characteristic (ROC) curve analysis, and a combined diagnostic model was constructed. Results: A total of 651 metabolites were detected, with 66 showing significant differences (P<0.05, VIP>1), mainly enriched in pathways such as unsaturated fatty acid synthesis and lysine degradation. Twelve metabolites (e.g., PC40:4|18:0_22:4, Val⁃Leu, Deoxyadenosine) had high diagnostic accuracy (AUC ≥0.85). The combined diagnostic model achieved an AUC of 1.00, demonstrating perfect discriminative ability. Conclusion: The plasma metabolite profile of IgAN pediatric patients undergoes significant changes, with notable alterations in lipid and amino acid metabolites. These 12 metabolites have high diagnostic accuracy and potential as non⁃invasive diagnostic biomarkers for IgAN.

Key words: IgA nephropathy, metabolomics, biomarkers, metabolic pathways