A comparative meta-analysis and in silico analysis on metabolomics Profiles in Nephrotic Syndrome for Biomarker Discovery

Nephrotic syndrome (NS) is a renal disorder characterized by excessive proteinuria, hypoalbuminemia, edema, and hyperlipidemia, which can lead to end-stage renal disease and require renal transplantation. Despite a growing number of NS metabolite profiling studies, there is a lack of consistency in their results. The aim of this meta-analysis was to identify a consensus hob panel of significantly dysregulated metabolites in NS that could serve as potential biomarkers. To achieve this, the Amanida package in the R environment was utilized on ۱۰ metabolome profiles obtained from ۷ human urine studies . The results panels comprised a volcano plot for quantitative results, a vote plot for the total up- or down-regulation behavior of each compound, and an explore plot of the vote-counting results. Subsequently, ۲۷ metabolites were determined to be dysregulated across ۶۵۰ samples. Among them, a panel of top meta-metabolites was introduced as biomarkers including up-regulated glucose and fumaric acid with a voting score of≥ ۴ and down-regulated Citric acid, Isobutyric acid, ۳-Hydroxyisovaleric acid, and Pyruvic acid with a voting score of ≤-۴. Subgroup analysis revealed ۳, ۷, and ۲ specific meta-metabolites in focal segmental glomerulosclerosis, membranous glomerulonephritis, and minimal change disease, respectively. Furthermore, enrichment analyses were performed with MetaboAnalyst (Version ۰.۴) for metabolite set enrichment analysis (MSEA) of the NS meta-metabolites . Enrichment analyses confirmed the involvement of various effective biological pathways in NS pathogenesis, such as the TCA cycle, and amino acids metabolisms. Moreover, in the constructed genemetabolite and metabolite-metabolite interaction network, citric acid, Pyruvic acid, and glucose were identified as hub metabolites worthy of further exploration as potential drug targets. In conclusion, the identified metabolites are potentially involved in the disease pathogenesis and could be evaluated as biomarkers or drug targets in NS.