Abstract: SA-PO0597
Urinary Extracellular Vesicles from Patients with Truncating Mutations Causing PKD Unmask Diagnostic, Prognostic, and Follow-Up Markers Associated with the Disease
Session Information
- Cystic Kidney Diseases: Clinical Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Pereira Hernández, María, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Vizoso, Marta, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Bravo, Susana, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Lago, Nerea, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Nuñez-Gonzalez, Laura, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Barcia de la Iglesia, Ana, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Diaz-Rodriguez, Candido, Hospital Clínico Universitario de Santiago de Compostela Servicio de Nefrología, Santiago de Compostela, La Coruña, Spain
- Vazquez, Carmen, Hospital Clínico Universitario de Santiago de Compostela Servicio de Nefrología, Santiago de Compostela, La Coruña, Spain
- Pardo, Maria, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Garcia-Gonzalez, Miguel A., Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
Background
Glycosaminoglycans (GAGs) are polysaccharide chains that interact with proteins and lipids forming the extracellular matrix, whose 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 enclosed in a lipid bilayer that are conservatively released by cells and whose cargo and membrane proteins reflect the cell of origin. Moreover, these molecules play an essential role in intercellular communication.
Our group has developed a method for the isolation of EVs in any type of biological sample (ExoGAG), already characterized 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.
Methods
Urine samples were collected from patients genetically diagnosed with polycystic kidney disease with truncating mutations in the PKD1 and PKD2 genes at different stages of the disease. Using ExoGAG, both vesicles and glycated proteins have been isolated and characterised by means of different proteomic, molecular, imaging and single-vesicle techniques.
Results
ExoGAG is a growing technology that has allowed us to identify a number of signaling pathways and proteins that are deregulated in urinary EVs in the context of ADPKD. Those proteins are mainly related to extracellular matrix, plasma membrane and extracellular vesicles and associated with the fibrinogen pathway. Moreover, based on these proteins, four candidate biomarkers for ADPKD have been identified in urine (under protection as P1, P2, P3 and P4) in patients with polycystic kidney disease, which are altered with disease progression, even in subclinical stages of renal damage.
Conclusion
The development of this new method for the isolation of the GAG-associated fraction in urine samples has allowed us to identify the molecular mechanisms underlying the disease as well as new biomarkers for prognosis/diagnosis/progression of renal diseases, based on the characterization of the glycoprotein and vesicular profile.
Funding
- Government Support – Non-U.S.