Abstract: SA-PO0611
Exome Sequencing in a Uruguayan Cohort Suspected of Hereditary Noncystic Nephropathies
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
- Yandian, Federico, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
- Spangenberg, Lucia, Institut Pasteur, Unidad Bioinformática, Montevideo, Uruguay
- Facal, Lucia, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
- Raggio, Víctor E., Universidad de la Republica Uruguay, Montevideo, Uruguay
- Dominguez, Maria Fernanda /F, Universidad de la Republica Uruguay, Montevideo, Uruguay
- Segarra, Jessica Marilud, Médica Uruguaya, Montevideo, Uruguay
- Boggia, Jose, Hospital de Clinicas Doctor Manuel Quintela, Montevideo, Uruguay
Background
Exome sequencing is increasingly utilized worldwide, leading to more accurate diagnoses of previously undetermined nephropathies and correcting misclassified cases. However, despite its growing importance, exome sequencing remains costly and often inaccessible to the general population.
Methods
Patients aged 16 years or older were included in the study if they had a personal and/or family history of chronic kidney disease (CKD), defined by at least one of the following criteria: an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2, persistent proteinuria > 0.3 g/day and/or microhematuria with > 5 red blood cells per high-power field. In the absence of a family history, index cases with corticosteroid-resistant nephrotic syndrome were also eligible for inclusion. Whole exome sequencing was performed on all enrolled patients for genetic analysis.
Results
A total of 77 patients were included in the study, of whom 68 (88.3%) were diagnosed with a genetic form of nephropathy. The most frequently identified genes were COL4A4 and COL4A5, each found in 32% of cases. Table 1 presents the variables associated with the development of kidney failure. The mean age at diagnosis of kidney failure was 37 ± 16 years. The presence of gross hematuria, persistent proteinuria, hearing loss, and prior use of immunosuppressive therapy were all significantly associated with the progression to kidney failure.
Conclusion
Next-generation sequencing has identified genetic causes in more than 600 genes associated with nephropathy, revealing monogenic etiologies in up to 30% of adults with chronic kidney disease (CKD), and in 12–56% of patients with CKD of unknown origin. These findings have important implications for treatment decisions, prognosis, and genetic counseling.
In this study, the percentage of positive results was higher compared to published data. This could be explained by the selection criteria utilized.
In countries with limited healthcare resources, implementing a pre-selection strategy to identify patients with a high likelihood of genetic kidney disease can significantly improve the diagnostic yield of genetic testing. This targeted approach may serve as a cost-effective strategy to optimize the use of genetic studies in resource-constrained settings.