Kidney Week

Abstract: TH-PO0624

APOL1 Genotype, Tubular Biomarkers, and Longitudinal Kidney Function Decline Among SPRINT Participants

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

• Lee, Adrian, University of California San Diego, La Jolla, California, United States

Adrian Lee

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz, PhD

• Wong, Angela, University of California San Diego, La Jolla, California, United States

Angela Wong

• Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States

Vasantha Jotwani, MD

• Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States

Michael Shlipak, MD, MPH

• Rifkin, Dena E., VA San Diego Healthcare System, San Diego, California, United States

Dena E. Rifkin, MD

• Bullen, Alexander L., VA San Diego Healthcare System, San Diego, California, United States

Alexander L. Bullen, MD, FASN

Background

Apolipoprotein A1 (APOL1) is an emerging etiology of kidney failure. However, only 15-20% of individuals with high-risk genotypes develop nephropathy. It is unclear whether tubular dysfunction biomarkers can help identify individuals with APOL1 who are at a higher risk of progression of kidney disease.

Methods

Among Systolic Blood Pressure Intervention Trial (SPRINT) participants of African ancestry with APOL1 genotyping and an eGFR under 60 ml/min/1.73m², we measured markers of tubular function (alpha-1 microglobulin [a1m], epidermal growth factor [EGF], uromodulin [uUMOD], secretion markers) and injury (urine clusterin, urine trefoil factor 3 [TFF3], Dickkopf-related protein 3 [DKK3], urine kidney injury molecule-1 [KIM-1], soluble tumoral necrosis factor receptors 1 and 2 [TNFR1 and TNFR2]) at baseline. Using multivariable adjusted linear regression, we evaluated the association between biomarkers and longitudinal eGFR decline by APOL1 genotype.

Results

Among 563 participants, 91 (16%) had 2 risk variants (RV). At baseline, participants with 2 RV had a worse tubular secretion score, lower uUMOD and EGF levels, and higher injury markers (TNFR1/2). Higher levels of TFF3 (B:-1.43, 95% CI -2.47, -0.40) and TNFR2 (B: -1.93, 95% CI -3.13, -0.72) were associated with faster eGFR decline among participants with 2 RV. Conversely, higher levels of EGF was associated sloweer decline (B: 4.78, 95% CI 3.12, 6.44), after adjusting for key risk factors, including baseline eGFR and albuminuria.

Conclusion

Among participants with APOL1 RV, tubular function and injury biomarkers can assist in the clinical prediction of eGFR decline, independent of baseline eGFR and albuminuria.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025bf22614c