Metabolomics Reveals Metabolic Alterations in Membranous Nephropathy and IgA nephropathy

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Background: Membranous nephropathy (MN) and IgA nephropathy (IgAN) are the most common primary glomerulopathies worldwide. The systemic metabolic changes in the progression of MN and IgAN are not fully understood. Methods: 87 MN patients, 70 IgAN patients, and 30 healthy controls were enrolled in this study. Untargeted metabolomics was performed to explore the differential metabolites and metabolic pathways in the early stage of MN and IgAN. ROC curve analyses were performed to judge the diagnostic ability of biomarkers. Results: PCA and OPLS-DA analysis suggested that obvious separation trend was obversed in both MN and IgAN patients from the healthy controls. 155 and 148 metabolites were identified significantly altered in MN and IgAN groups. Of these, 70 metabolites were markedly altered in both disease groups and 6 metabolites showed the opposite tendency, including L-tryptophan, L-kynurenine, gamma-aminobutyric acid (GABA), indoleacetaldehyde, 5-hydroxyindoleacetylglycine, and N-alpha-acetyllysine. The most affected metabolic pathways includes the amino acid metabolic pathways, citrate cycle, pantothenate and CoA biosynthesis, and hormone signaling pathways. Conclusion: Great metabolic disorders had happened during the progression of MN and IgAN. L-tryptophan, L-kynurenine, gamma-aminobutyric acid (GABA), indoleacetaldehyde, 5-hydroxyindoleacetylglycine, and N-alpha-acetyllysine may show potential as biomarkers for for identification of MN and IgAN.