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APOL1-Mediated Kidney Disease

People who have a specific form of the APOL1 gene are at a higher risk for developing kidney disease. When kidney disease is caused by the APOL1 gene, it is considered APOL1-mediated kidney disease. Having the disease-causing form of the APOL1 gene does not always result in kidney disease. About 1 in 5 people with this gene eventually develop kidney disease.1,2

The role of the APOL1 gene

Genes are made up of DNA that contains all the information your body needs to function. Each cell in your body uses certain genes to make proteins for different functions. The APOL1 (apolipoprotein L1) gene makes the APOL1 protein.1,2

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One of the functions of the APOL1 protein is to carry good cholesterol (HDL) through your blood. A healthy amount of cholesterol is needed for our bodies to function normally. Proteins like APOL1 bind to cholesterol. This allows the cholesterol to travel through the bloodstream and reach different areas of the body.1,2

The APOL1 protein also plays a role in our immune system. This system helps fight infections.1,2

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The APOL1 gene and kidney disease

Some people have a version of the APOL1 gene with a few changes. These changes are also called mutations. There are 2 mutated versions of the APOL1 gene that have been linked to kidney disease. These are called G1 and G2 variants.1,2

In the G1 variant, a small part of the DNA of the APOL1 gene is changed. In the G2 variant, a small part of the APOL1 gene is missing. Having these mutated versions of the APOL1 gene can put you at a higher risk for kidney disease.1,2

Our cells have 2 copies of every gene, 1 from each parent. If both copies of your APOL1 gene are the mutated versions (either G1 or G2), then you are at higher risk for APOL1-mediated kidney disease. People who have at least 1 healthy copy of the APOL1 gene are not at a higher risk.2

We do not know exactly how these mutated APOL1 genes increase the risk of developing kidney disease. Also, we don’t know what role APOL1 proteins play when it comes to normal kidney function. Research suggests that the G1 and G2 variants create abnormal APOL1 protein. This abnormal protein can damage cells, especially kidney cells. Research in this area is ongoing.1,2

Who is more likely to have APOL1-mediated kidney disease?

People who have ancestors from Western or Central Africa are more likely to have the G1 or G2 variants of the APOL1 gene. Scientists believe that the mutated APOL1 gene is a form of protection against an infection caused by a parasite. This parasite is mostly found in Western or Central African countries. People from these regions might identify as:1-3

  • Black
  • African American
  • Afro-Caribbean
  • Hispanic
  • Latina/Latino

In the United States, 13 percent of Black people have 2 copies of the mutated version of the APOL1 gene. About 20 percent of people who have the mutated copies of APOL1 gene end up developing kidney disease.1,2

Treatments for APOL1-mediated kidney disease

As of this writing, there is no cure for APOL1-mediated kidney disease. Most treatments aim to manage your symptoms and try to prevent further kidney damage. Your doctor may prescribe certain drugs that try to slow down or stop kidney damage.3

There is 1 drug being tested that specifically targets the underlying cause of APOL1-mediated kidney disease. This drug is called VX-147. VX-147 stops the APOL1 protein from damaging the kidneys by blocking its function. As of 2024, this drug is undergoing clinical trials to find out how well it works and its possible side effects.4

Genetic testing is the only way to know if you have the APOL1 gene that puts you at a higher risk for kidney disease. Discuss with your doctor if you think you will benefit from genetic testing, especially if you have a family history of kidney disease. Things that can help prevent or delay kidney disease include:2

  • A healthy diet
  • Exercise
  • Regular check-ups with your doctor

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In addition to chronic kidney disease, do you also live with diabetes?

Treatment results and side effects can vary from person to person. This treatment information is not meant to replace professional medical advice. Talk to your doctor about what to expect before starting and while taking any treatment.

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