Comparative urine proteomics and metabolomic analysis of renal AA amyloidosis and correlation with clinopathologic scores

Bioinformatic analysis of proteomic and metabolomic studies is critical in terms of diagnostic and prognostic aspects and no urinary omics analysis has been reported in renal AA amyloidosis patients. The aim of this study is to perform comparative urine proteomics and metabolomics analysis in renal AA amyloidosis. Urine samples of 8 newly diagnosed AA Amyloidosis (AA), 8 Membranous Nephropathy (MN), 8 IgA Nephropathy (IgAN), 7 Focal Segmental Glomerulosclerosis (FSGS) patients with control groups were collected. Proteomic analyzes were performed with nLC-MS/MS-QTOF in the AA, MN and control groups; and metabolomic analyzes were performed by GC/MS in all patients. Pathological specimens were scored according to tubular atrophy (TA) and interstitial fibrosis (IF) grades. As a result of proteomic analysis, epithelial growth factor, megalin, cubulin and cadherins were observed among 51 proteins whose levels were significantly lower in the AA group compared to the control group. While uromodulin was lower in the AA group than in the MN group; ribonuclease 1 and α-1-microglobulin were observed at higher levels in the AA group. In Gene Ontology (GO) analysis, the biological processes with the highest fold enrichment value were digestion and homophilic cell adhesion. Myo-inositol and urate were higher in the AA compared to MN, while D-mannitol and N-acetylglutamic acid were higher in the AA compared to control group in metabolomic analysis. IF and TA scores were higher in the AA compared to other groups (median 2, [3-0]). In our comparative urine omics analysis, the main molecules that distinguish the AA amyloidosis were associated with high tubulointerstitial damage. In addition, network and GO analyzes indicated downregulate adhesion proteins between tubule cells, suggesting a possible increased urinary shear stress. Keywords: AA Amyloidosis, Proteomics, Metabolomics, Uromodulin, α-1-microglobulin Supporting Organizations: Turkish Hypertension and Kidney Diseases Association