Untargeted Serum Metabolomics of Patients with Immunoglobulin A Nephropathy Using Gas Chromatography-Mass Spectrometry

The metabolome as a set of metabolites reflects the systemic physiological state of the organism and is the endpoint of cellular activity, reflecting the contribution of upstream biological regulatory processes, genome, epigenome, transcriptome, and proteome, as well as environmental factors, thereby linking genotype to phenotype. For this reason, determining a wide range of small molecules in biological fluids is becoming an increasingly important approach in studying pathophysiological processes. Due to the unique ability to access extensive databases of human metabolite mass spectra, gas chromatography-mass spectrometry (GC-MS) is one of the key methods used in metabolomic analysis. This work presents a pilot untargeted metabolomics study of blood serum from 10 patients with clinically and morphologically confirmed primary immunoglobulin A nephropathy (IgAN) in the active stage and 9 volunteers without signs of kidney pathology. Serum samples were analyzed by GC-MS. Interpretation of mass spectrometry data, annotation and identification of metabolites were carried out using the NIST20 library, the HMDB database, and analytical standards. After performing multi-step data preprocessing and normalization, chemometric analysis was conducted using multivariate statistical methods. The statistical reliability of the model was confirmed by cross-validation. Statistically significant changes in the levels of 20 metabolites were detected in the blood serum of IgAN patients compared to the control group. A decrease in the content of a number of amino acids (serine, methionine, tyrosine, tryptophan), as well as the microbial tryptophan metabolite indole-3-propionic acid, was found, along with an increase in the content of some mono- and disaccharides and uric acid, during the active phase of IgAN. The obtained results indicate profound disorders in key metabolic pathways, including energy metabolism, amino acid metabolism, and peroxidation processes, associated with alterations in the intestinal microbiome as a probable factor in the development and progression of the disease.