Abstract: SA-PO0633
Urine-Derived Renal Epithelial Cells: A Noninvasive Tool for Diagnosing and Monitoring Kidney Involvement in Fabry Disease
Session Information
- Monogenic Kidney Diseases: Tubular and Other
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
- Sayer, John Andrew, Newcastle University, Newcastle upon Tyne, England, United Kingdom
- Sentell, Zachary T., Newcastle University, Newcastle upon Tyne, England, United Kingdom
- Dhondurao Sudhindar, Praveen, Newcastle University, Newcastle upon Tyne, England, United Kingdom
- Arcila Galvis, Juliana Estefania, Newcastle University, Newcastle upon Tyne, England, United Kingdom
Background
Fabry Disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency, leading to glycosphingolipid accumulation and progressive organ damage. Kidney involvement is a major complication, yet diagnosis often requires invasive kidney biopsy, and follow-up relies on indirect biomarkers or imaging, which lack cellular and molecular resolution. Here, we present human urine-derived renal epithelial cells (hURECs) as a minimally invasive alternative for phenotyping renal Fabry disease and monitoring treatment response
Methods
Using hURECs from a newly diagnosed male Fabry disease patient, transmission electron microscopy (TEM) revealed lysosomal inclusions diagnostic of renal Fabry pathology, consistent with kidney biopsy findings. Bulk RNA sequencing (RNAseq) identified a transcriptomic disease signature including dysregulated pathways involved in lipid metabolism homeostasis, ion transport, endoplasmic reticulum stress response, and collagen processing.
Results
Bulk RNA sequencing (RNAseq) identified a transcriptomic disease signature including dysregulated pathways involved in lipid metabolism homeostasis, ion transport, endoplasmic reticulum stress response, and collagen processing. Following systemic treatment of the patient with chaperone therapy, partial amelioration of the hUREC transcriptomic signature was observed during the first few months. However, by nine months, the signature began reverting towards baseline, correlating with continued kidney function decline. This prompted a transition to enzyme replacement therapy (ERT), with early evaluations showing transcriptomic stabilization.
Conclusion
Our findings demonstrate that hURECs replicate key structural and molecular markers of renal Fabry disease and offer a non-invasive platform for longitudinal assessment of treatment response. TEM of hURECs provides a diagnostic alternative to biopsy, while RNAseq-based transcriptomic profiling offers a sensitive and dynamic view of molecular changes, including key dysregulated pathways. This dual utility positions hURECs as a novel tool for improving the diagnosis, monitoring, and personalized management of renal involvement in Fabry disease.
Funding
- Commercial Support – Sanofi