Kidney Week

Abstract: TH-PO0623

APOL1 Risk Variants and Progression of CKD: A CRIC Follow-Up Study

Session Information

• Genetic Diseases of the Kidneys: Complex Kidney Traits
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits

Authors

• Tewari, Sakshi, The University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, United States

Sakshi Tewari, MHS

• Parsa, Afshin, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Afshin Parsa, MD, MPH, FASN

• Ricardo, Ana C., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

Ana C. Ricardo, MD, MS, MPH, FASN

• Hsu, Chi-yuan, University of California San Francisco School of Medicine, San Francisco, California, United States

Chi-yuan Hsu, MD, MS, MSc, FASN

• Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States

Hernan Rincon-Choles, MD, MS, FASN

• Weir, Matthew R., University of Maryland, College Park, Maryland, United States

Matthew R. Weir, MD

• Sondheimer, James H., Wayne State University School of Medicine, Detroit, Michigan, United States

James H. Sondheimer, MD, FASN

• Muiru, Anthony N., University of California San Francisco School of Medicine, San Francisco, California, United States

Anthony N. Muiru, MD, MPH

• Appel, Lawrence J., Johns Hopkins Medicine, Baltimore, Maryland, United States

Lawrence J. Appel, MD, MPH

• Anderson, Amanda Hyre, The University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, United States

Amanda Hyre Anderson, PhD, MPH, FASN

• Lash, James P., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

James P. Lash, MD, FASN

• Franceschini, Nora, The University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, United States

Nora Franceschini, MD, MPH

Group or Team Name

• CRIC Investigators.

Background

In 2013, we showed that APOL1 risk variants are a risk factor for renal events in the Chronic Renal Insufficiency Cohort (CRIC). Here we evaluate the risk over extended follow-up after accounting for genetic background risk using estimated Glomerular Filtration Rate (eGFR) polygenic risk scores (PRS).

Methods

CRIC participants enrolled between June 2003 and August 2008 were included if they self-reported being White or Black race and had available APOL1 genotype and event-time data. The composite renal event was end stage renal disease, or a ≥50% drop in baseline eGFR. Our exposure was defined using APOL1 G1/G2 genotype data in Black participants as AA high-risk (2 copies), AA low-risk (0/1 copies) with White participants as reference. eGFR PRS were modeled as z-scores. Proportionality and functional form assumptions were checked via Schoenfeld and Martingale residuals. Multivariable cox regression was used to estimate Hazard Ratios (95% CI).

Results

Of 2792 participants at baseline, 1140 (40.8%) had a renal event over a median follow-up of 7.0 (3.2, 12.7) years. Renal event rates (per 100 PY) increased with APOL1 categories (3.7, 6.8, 9.0). In adjusted models, Black individuals with high or low-risk genotypes had greater risk of a renal event compared to White participants, independent of eGFR PRS, demographic, clinical and behavioral variables. Models were stratified by diabetes status to compare non-diabetic participants to diabetic (aHR_{APOL1(2 copies)} = 2.01 vs 1.72, aHR_{APOL1(0/1 copies)} =1.63 vs 1.37). Model improvement by eGFR PRS was negligible (△C-index<1%).

Conclusion

APOL1 risk variants are associated with long-term risk of a renal event in CRIC. Genetic background risk provides no additional risk discrimination.

Kaplan Meier curve for time to renal event, by APOL1 and diabetes

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025x1gwchb1