Kidney Week

Abstract: TH-PO0564

Genetic Ancestry as a Lens on ESKD Risk

Session Information

• CKD: From Global Burden to Precision Care - Epidemiology, Demographics, Geographies, and Risk Factors
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

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

Darbey Raible, MS

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

Uma Arora, PhD

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

Dinah Clark, MS

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

Michelle Bloom, PhD

• Suresh, Niraja, Natera Inc, Austin, Texas, United States

Niraja Suresh, 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

CKD and ESKD disproportionately affect African Americans and Hispanic/Latino populations with them bearing the highest burden across racial/ethnic groups. Risk in African Americans is partly driven by APOL1, but contributors to CKD progression in Hispanic/Latino individuals are poorly understood. We assessed factors associated with progression to ESKD in a CKD cohort stratified by genetic ancestry.

Methods

Genetic ancestry was inferred using EthSEQ in a real-world database of individuals tested with a broad kidney disease genetic panel (RenasightIQ^TM) linked to a repository of open/closed claims, EHR and social determinants of health data (Forian's Hybrid data ecosystem, CHRONOS^TM). Ancestry categories were African (AFR), European (EUR), Admixed American (AMR), or East/South Asian (E/SAS). Positive genetic results were defined as ≥1 P/LP variant in autosomal dominant/X-linked genes, ≥2 in autosomal recessive genes, or APOL1 dual risk variants (DRV); no APOL1 risk variants (G0) were classified as NRV. ESKD-free survival (i.e. time to ICD-10 N18.5/N18.6, eGFR <15, dialysis, or transplant) was assessed.

Results

Among 164,031 individuals with genetic ancestry and self-reported race/ethnicity, 11.2% were discordant, with 9.2% (4,775/51,947) of AFR individuals not identifying as African American/Black and 13.9% (3,599/25,961) of AMR individuals not identifying as Hispanic/Latino.

Risk of progression to ESKD was highest in AMR (HR: 1.75 vs EUR; p<0.001). Genetic positivity ranged from 21.6% (AMR) to 34.3% (AFR). Among those with negative genetic results, AMR individuals had the highest ESKD odds (OR 2.24). APOL1-DRV was present in 21.8% of AFR and 1.05% of AMR individuals (86% of non-AFR DRV). In AMR, APOL1-DRV was associated with increased odds of ESKD (OR 3.17) and FSGS (OR 4.60). Risk of ESKD was indistinguishable between AMR APOL1-NRV and AFR APOL1-DRV (HR 0.96; p=0.20).

Conclusion

AMR individuals had the highest risk of progression to ESKD, with those lacking APOL1 risk alleles at comparable risk to AFR individuals with high-risk genotypes. Discordance between self-reported race/ethnicity and genetic ancestry, and differences across ancestries, highlight limitations of self-reporting in capturing risk. These findings suggest additional ancestral factors contribute to CKD progression, including in genetic disease. Genetic testing is essential for identifying established risk factors and improving stratification as additional contributors are defined.

Funding

• Commercial Support – Natera, Inc.