Abstract: SA-PO0162
Etiological Profile and Polygenic Risk Scores in Patients with Advanced CKD: Insights from a Sardinian Tertiary Center
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Angioi, Andrea, Azienda Ospedaliera Brotzu, Cagliari, Sardinia, Italy
- Piras, Doloretta, Azienda Ospedaliera Brotzu, Cagliari, Sardinia, Italy
- Masala, Marco, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Cara, Michele, Azienda Ospedaliera Brotzu, Cagliari, Sardinia, Italy
- Zoledziewska, Magdalena, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Pitzalis, Maristella, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Fiorillo, Edoardo, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Pala, Mauro, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Sidore, Carlo, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Mulas, Antonella, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Argiolas, Davide, Azienda Ospedaliera Brotzu, Cagliari, Sardinia, Italy
- Maxia, Stefania, Azienda Ospedaliera Brotzu, Cagliari, Sardinia, Italy
- Lepori, Nicola, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Floris, Matteo, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Cabiddu, Gianfranca, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Cucca, Francesco, Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
- Pani, Antonello, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
Background
A substantial proportion of advanced chronic kidney disease (CKD) cases remains of unknown etiology despite routine clinical evaluation. Polygenic risk scores (PRS) have been proposed as tools for genetic risk stratification in CKD, but their performance in real-world end-stage cohorts remains poorly characterized.
Methods
Observational study of 277 patients with advanced CKD (97.1% on renal replacement therapy) followed at a tertiary nephrology center (ARNAS Brotzu, Cagliari, IT). Clinical data were collected from medical records; blood samples were prospectively obtained for genetic analysis. Renal phenotype was assigned based on clinical, histological and/or genetic criteria into 9 categories. Genome-wide genotyping with imputation was performed; PRS for eGFR were calculated and compared to 4745 Sardinian blood donors as controls.
Results
The cohort was 64.4% male, mean age 59.6±15.0 years. Unknown etiology was the most frequent phenotype (33.9%), exceeding the 10–20% commonly reported in European CKD/ESKD cohorts. Recognized congenital/monogenic nephropathies accounted for 16.2% (including ADPKD and other rare forms). Cardiovascular comorbidities were prevalent (hypertension 93.5%; carotid atherosclerosis 40.8%; diabetes mellitus 27.4%). PRS for eGFR showed no significant difference between cases and controls (p=0.541) and did not discriminate across etiological subgroups.
Conclusion
In this advanced CKD cohort, unknown etiology is strikingly more prevalent than in other European series, suggesting late specialist referral and/or a high burden of unrecognized genetic disease. The limited discriminative ability of PRS for eGFR may reflect the advanced disease stage, where etiological heterogeneity and unrecognized monogenic disease may dilute polygenic signals. These findings support earlier etiological workup including genetic diagnostics before irreversible renal function loss.
Funding
- Government Support – Non-U.S.