Kidney Week

Abstract: TH-OR064

Genetic Diagnoses Across Clinical Presentations of Glomerular Diseases

Session Information

• Glomerular Diseases: Epidemiology and Real-World Outcomes
  October 22, 2026 | Location: Room 501, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Arora, Uma, Natera Inc, Austin, Texas, United States

Uma Arora, PhD

• Clark, Dinah, Natera Inc, Austin, Texas, United States

Dinah Clark, MS

• Raible, Darbey, Natera Inc, Austin, Texas, United States

Darbey Raible, MS

• Bloom, Michelle, Natera Inc, Austin, Texas, United States

Michelle Bloom, PhD

• Schneider, Ronen, Natera Inc, Austin, Texas, United States

Ronen Schneider, MD

• Andrews, Stephen, Natera Inc, Austin, Texas, United States

Stephen Andrews, PhD

• Lazar, Andrew, UH Cleveland Medical Center, Cleveland, Ohio, United States

Andrew Lazar, MD

Background

Glomerular diseases (GD) have diverse clinical presentations, etiologies and prognoses. Manifestations such as hematuria, proteinuria, and focal segmental glomerulosclerosis (FSGS) can overlap across GD, but do not indicate etiology. Identifying causal mechanisms through genetic testing has prognostic and therapeutic value but is not routinely used early in clinical evaluation.

Methods

Retrospective analysis of a real-world database of broad kidney disease genetic panel results (RenasightIQ^TM) linked with a repository of open/closed claims, EHR, and social determinants of health data (Forian’s Hybrid data ecosystem, CHRONOS^TM) identified patients with GD presentations: hematuria (ICD-10 R31), proteinuria (R80), FSGS (N00.1-N08.1) or GD (N00-N08, excluding FSGS). Positive genetic results were ≥1 P/LP variant in autosomal dominant/X-linked genes, ≥2 in autosomal recessive genes, or APOL1 dual risk variants (DRV). Genetic findings, eGFR decline, and ESKD-free survival were compared.

Results

Among 117,666 individuals with GD presentations, those with FSGS and GD had the fastest adjusted eGFR decline, and those with FSGS had the highest risk of progression to ESKD (Table).

Across GD presentations, 25.9% (31,477/117,666) of individuals had positive genetic findings, with the highest diagnostic yield in FSGS (34.0%). While genetic etiologies varied by presentation, most positive findings (59.1%) involved COL4A3/4/5, other monogenic GD genes, or APOL1-DRV. Among genetically positive individuals, FSGS was present in 24% with APOL1-DRV, 40% with monogenic GD, and 8% with COL4A3/4/5 variants.

Conclusion

Genetic etiologies were common in GD, with varying distributions across presentations. These findings support genetic testing across the GD clinical spectrum. Etiologic identification in patients with proteinuria or hematuria can improve risk stratification, help determine management and biopsy strategies, minimize the use of ineffective treatments, and ensure the timely initiation of targeted therapies. Such interventions are crucial before patients progress to FSGS or GD, clinical groups that exhibit rapid eGFR loss and an elevated risk of ESKD.

Table: Outcomes and Genetic Yield Across GD Presentations

Funding

• Commercial Support – Natera, Inc.