Abstract: TH-PO0580
Urinary Proteomics in Alport Syndrome to Identify Rapid Progressors
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 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
- Goma-Garces, Elena, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Sanchez Niño, Maria Dolores, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Sanz, Ana Belen, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Byrska, Julia Klaudia, Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Pilco Teran, Melissa, Fundacio Puigvert, Barcelona, CT, Spain
- González Toledo, Beatriz, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Furlano, Monica, Fundacio Puigvert, Barcelona, CT, Spain
- Torra, Roser, Fundacio Puigvert, Barcelona, CT, Spain
- Ortiz, Alberto, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
- Pérez Gómez, María Vanessa, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Community of Madrid, Spain
Background
The clinical presentation of Alport syndrome (AS) is very variable. Early identification of rapid progressors will allow patient selection for clinical trials and for early intervention. Proteomics enables large-scale profiling of urinary proteins, offering a non-invasive window into kidney disease pathophysiology and risk stratification. We aimed to identify urinary protein expression patterns associated with progression of AS.
Methods
Cross-sectional multicenter study in 88 genetically confirmed AS patients (mean age 60±14 years): rapid (n=40) and slow (n=48) progressors based on GFR slopes, proteinuria and age. Morning urine was analyzed using OLINK targeted proteomics. Protein abundance values were normalized to urinary creatinine. Groups were compared using a two-sided Wilcoxon test with FDR correction (q <0.05). Bioinformatic pathway enrichment analysis was performed for differentially expressed proteins.
Results
22 urinary proteins significantly differed between rapid and slow progressors, 20 upregulated and 2 downregulated in rapid progressors. Most differential proteins were involved in extracellular matrix production, intercellular adhesion, repair, namely, pathways implicated in the pathogenesis of the disease. Additionally, we observed enrichment of immune-related pathways, including complement activation, cytokine signaling, and TNF-α signaling. Some enriched pathways have been previously associated with the pathogenesis of autoimmune nephropathies, such as IgA nephropathy and lupus nephritis. Nonbiased clustering of urinary protein biomarkers identified a subgroup of rapid progressors with more advanced CKD despite statistically similar (numerically lower) proteinuria.
Conclusion
Although AS is a monogenic disorder, our findings suggest that immune and inflammatory mechanisms may contribute to disease progression and may help to stratify the risk of CKD progression. These findings raise the possibility that immunomodulatory therapies could slow CKD progression in AS patients and may guide the design of preclinical intervention studies.
Funding
- Private Foundation Support