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APOL1 Mediated Kidney Disease: A Review and Look Toward the Future

Vinay Srinivasan1, Paolo Nikolai So2, Edward P K Kwakyi3

  • 1Division of Nephrology, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ.

Kidney Medicine
|August 21, 2025
PubMed

Insights

Genetic factors like APOL1 risk alleles contribute to kidney disease disparities in people of African ancestry. Understanding these genetic links and potential triggers is key for developing targeted treatments and genetic testing strategies.

Area of Science:

  • Nephrology
  • Genetics
  • Epidemiology

Background:

  • Individuals of recent African ancestry experience disproportionately high rates of kidney disease.
  • The discovery of Apolipoprotein L1 (APOL1) gene risk alleles (G1 and G2) offers insights into these health disparities.
  • APOL1 high-risk alleles may provide evolutionary protection against Trypanosoma parasites but are linked to kidney disease in certain populations.

Purpose of the Study:

  • To review the development and clinical implications of APOL1 risk alleles in kidney disease.
  • To discuss the 'second hit' hypothesis involving genetic, environmental, and inflammatory factors.
  • To propose a framework for nephrologists regarding APOL1 genetic testing.

Main Methods:

  • Review of scientific literature on APOL1 gene, risk alleles, and kidney disease.
  • Discussion of cellular toxicity mechanisms and therapeutic targets.
  • Analysis of clinical trial data, including inaxaplin's progression to Phase 3.

Main Results:

  • Approximately 6 million African Americans possess a high-risk APOL1 genotype.
  • Not all individuals with high-risk genotypes develop kidney disease, suggesting additional contributing factors.
  • Targeted therapies like inaxaplin are being investigated for APOL1-associated kidney disease.

Conclusions:

  • APOL1 risk alleles are significant contributors to kidney disease disparities.
  • Further research into genetic, environmental, and inflammatory triggers is crucial.
  • Accessible genetic testing and targeted therapies hold promise for managing APOL1-related kidney disease.

Keywords:
APOL1African ancestrygenetic testingkidney diseaserisk variants

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