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Abstract: TH-PO0740

Multicenter, Observational, Cross-Sectional Study to Estimate the Frequencies of APOL1 Genetic Variants in Adult Black and African American Patients with Proteinuric Kidney Disease

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Limb, Susan, Maze Therapeutics Inc, South San Francisco, California, United States
  • Chung, Bernard, Maze Therapeutics Inc, South San Francisco, California, United States
  • Alcantar, Oscar, Maze Therapeutics Inc, South San Francisco, California, United States
  • Naderi, Neda, Maze Therapeutics Inc, South San Francisco, California, United States
  • Satterfield, Terry, Maze Therapeutics Inc, South San Francisco, California, United States
  • Ullman, Julie, Maze Therapeutics Inc, South San Francisco, California, United States
  • Assimon, Victoria, Maze Therapeutics Inc, South San Francisco, California, United States
  • Hoek, Maarten, Maze Therapeutics Inc, South San Francisco, California, United States
  • Bernstein, Harold S., Maze Therapeutics Inc, South San Francisco, California, United States
Background

Black and African-American populations face a high burden of kidney disease. Two common apolipoprotein L1 (APOL1) high-risk genetic variants, G1 and G2, have been identified in individuals of African ancestry, with carriers being at increased risk for different types of kidney disease and/or more rapid disease progression. MZE829-801 is a genotyping and biomarker study evaluating the frequencies of APOL1 genetic variants in individuals of African ancestry with proteinuric kidney disease.

Methods

The U.S.-based multicenter, observational, cross-sectional study will enroll adults of self-identified African ancestry, ages 18 to 65, with chronic kidney disease (CKD) and proteinuria documented within the last 12 months, (UPCR >0.2 g/g, UACR >30 mg/g, or 2+ urine dipstick protein). Eligible participants will provide blood and urine samples for APOL1 genotyping, renal function, and exploratory biomarker analyses, with an optional genetic counseling visit.

Results

As of 01May2025, a total of 188 participants have been genotyped at 23 sites located throughout the U.S. The mean age was 53.5 years (19-65 range), and 93 (49%) and 95 (51%) were female and male, respectively. A total of 34 (18%) were identified to carry 2 APOL1 high-risk genetic variants. The distribution of the APOL1 genotypes is as follows: G1/G1 9%, G1/G2 6%, G2/G2 3%, G0/G1 35%, G0/G2 11%, and G0/G0 36%. The study is in progress, and updated results will be presented.

Conclusion

The observed high frequency of APOL1 high-risk genotypes in this CKD population with proteinuria and self-identified African ancestry, aligns with prior reports, supporting the adoption of genotype testing in clinical practice to stratify risk and determine prognosis. Identifying these individuals and collecting samples will enable analyses of additional biomarkers and potentially disease-modifying genotypes, to identify mediators of disease severity in APOL1 kidney disease.

Funding

  • Commercial Support – Maze Therapeutics

Digital Object Identifier (DOI)