Advanced proteomics MALDI-MSI imaging in chronic glomerulonephrites: from diagnostics to precision medicine

Chronical kidney disease (CKD) is a worldwide health problem with increasing incidence, where the major part accounts for chronic glomerulonephrites (GN). It is a group of diseases of various aetiology and multiform clinical course, having various prognosis which is often hardly predictable as well as existing prognostic markers are not always certain. There is an urging need of new reliable and specific prognostic and therapeutic markers research. A modern proteomic technology - Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been employed in many GN studies showing promising results. We aimed to study several forms of primary and secondary glomerulonephrites (membranous nephropathy, IgA nephropathy, diabetic nephropathy) to enlighten possible molecular alterations significant of diseases’ progression. The studies were performed on renal tissue biopsies, analysing them with high spatial resolution MALDI-MSI to get better visualisation of signals’ co-localisation on tissue. We performed a comparison of molecular profiles of various forms of GN. As a result, we were able to generate and distinguish specific tryptic peptides profiles of different cell regions (tubules, glomeruli, interstitium, connective tissue) and detect proteins with an altered intensity, implicated in inflammatory and healing pathways. MALDI-MSI, being able to define renal structures, could provide additional diagnostic and prognostic information. Generation of collective diagnostic panels may fulfil our pathogenesis understanding and assist clinical prognostic assessment.