#118 The new era of glycomics for the identification of prognostic and diagnostic biomarkers of kidney disease: ExoGAG

Abstract Background and Aims Glycosaminoglycans (GAGs) are large polysaccharides formed by repeated sequences of disaccharides that interact through glycosidic bonds with proteins and lipids, forming the extracellular matrix. The glycosylation state is altered as a consequence of different pathologies, such as cancer or kidney disease. GAGs are also present in extracellular vesicles (EVs), nanometric structures bounded by a lipid bilayer that are conservatively released by cells and whose cargo (RNA/miRNA, DNA and proteins) and membrane proteins is a reflection of the cell of origin. Moreover, these molecules play an essential role in intercellular communication. Our group has developed a method for the isolation of GAGs, glycoproteins and EVs in any type of biological sample, called EXOGAG (marketed by Nasas Biotech), currently already characterised in urine, breast milk and plasma. This method has allowed us to identify new prognostic and diagnostic biomarkers of disease in autosomal dominant polycystic kidney disease (ADPKD), the most prevalent hereditary kidney disease. Method urine samples have been collected from patients genetically diagnosed with polycystic kidney disease type I and type II at different stages of the disease. Using ExoGAG, both vesicles and glycated proteins have been isolated and characterised by means of different proteomic techniques (Western Blot, Mass Spectrometry), image characterisation (Electron Microscopy and Immunofluorescence) and vesicle component analysis (ExoView® or Nanoparticle Tracking Analysis®). Results ExoGAG is a growing technology that has allowed us to identify a series of biomarkers in urine (in protection) in patients with polycystic kidney disease, which are altered with the progression of the disease, even anticipating currently used markers of loss of function or renal damage. We are currently continuing to explore its potential in other types of liquid biopsies, having optimised the protocols for breast milk and plasma as well. Conclusion The development of this new method for isolating the GAG-associated fraction in urine samples has allowed us to identify new prognostic/diagnostic biomarkers of kidney disease, based on the characterisation of the glycoprotein and vesicular profile. This study opens the door to the new era of glycomics in kidney disease.