Everyone has two copies of the APOL1 (Apolipoprotein L1) gene. Genes are a part or your DNA and tell your body which proteins to create. The APOL1 gene creates proteins that play a role in immunity, our body's built-in system to fight threats. Some individuals have a mutation (a change or variation) in one or both of the APOL1 genes. This mutation is associated with increased protection from a parasite that causes African sleeping sickness. Unfortunately, while protecting from one disease, the APOL1 gene mutation has been shown to increase the risk for significant kidney damage in some. People who inherit mutations in both of their APOL1 genes have a higher chance of developing kidney disease including, but not limited to, focal segmental glomerulosclerosis (FSGS).
What is the APOL1 gene and how does it cause kidney disease?
The APOL1 gene makes a protein in your immune system which is your body's cells and tissues that fight infection. Genes are in the part of your cells that contain DNA. You have two copies of each gene: one from each of your parents. Genes are passed down from parents to children, including genes that have mutations (a change or variation).
Everyone has the two APOL1 genes. Normally, the APOL1 genes make a helpful immune system protein. Some people are born with mutations in one or both APOL1 genes. If you inherit mutations in both APOL1 genes, you have an increased risk for developing kidney disease. The inherited APOL1 mutations can:
- Cause damage to parts of the kidney that filter blood
- Sometimes cause cells in the kidney to die, which leads to damage and scarring in the kidneys and can lead to kidney failure
For example, if you inherit a mutation in both copies of the APOL1 gene, you have a 10 times higher chance of having a type of kidney disease called focal segmental glomerulosclerosis (FSGS) than people without the gene mutation. FSGS is a rare type of kidney disease that causes scarring (sclerosis) in the filters of your kidneys. Scarring can make it harder for the kidneys to filter waste. Doctors may call it APOL1-mediated kidney disease or APOL1-mediated FSGS. APOL1-mediated FSGS causes damage to the kidneys in a short time, and can lead to kidney failure much faster, than other types of FSGS.
Who is more likely to have a mutation in the APOL1 gene?
The APOL1 gene evolved over the past 3,000-10,000 years in people who lived in Western and Central Africa. The mutation that evolved is associated with protection against a certain type of parasite that causes African sleeping sickness. As a result, you are more likely to have APOL1 gene mutations if you are from Western or Central Africa or have an ancestor who came from these regions. This includes people who identify as:
- African American
If you have two of the APOL1 genetic mutations, you are at a higher risk for developing kidney disease and even kidney failure. In the United States, an estimated 13% of Black Americans have two of the APOL1 genetic variations. However, not everyone who has two copies of APOL1 genetic mutations will get kidney disease. If you have mutations in both copies of the APOL1 gene, there is a 1 in 5 chance that you will go on to develop kidney disease.
Black people with kidney disease are more likely to develop kidney failure than any other racial/ethnic group. Research of the APOL1 genetic mutation and the substantially increased risk for kidney disease among impacted Black people has helped to improve understanding of the kidney disease disparities in this population.
What are the symptoms of kidney disease?
If you have APOL1 gene mutations that cause damage to your kidneys you may not have any symptoms of kidney disease until your kidneys are close to failing. As your kidney damage gets worse, you may notice one or more of these symptoms:
- Protein in your urine (pee)
- Swelling in your legs or weight gain
- Feeling weak and tired
- High blood pressure
If you have these symptoms or have family members who have kidney disease, talk to your doctor about getting tested for kidney disease. Remember, the only way to know how well your kidneys are working is to get tested.
How will I know if I have APOL1 gene mutations?
The only way to know if you have the APOL1 gene mutations is to do genetic testing. This testing would look for gene mutations with a sample of blood or saliva (spit).
You or your doctor may consider genetic testing if you have kidney disease and do not know the cause or if you are considering donating a kidney. You may also consider testing if you know a family member is a carrier for the APOL1 gene mutation.
Your doctor can order the genetic test or send you to a genetic counselor (a health care professional with specific training in genetics and counseling). If you have questions about genetic testing talk with your doctor about your options or ask for a referral to a genetic counselor to learn more information.
If you have kidney failure and are considering a transplant, you may consider having your donor get screened for the APOL1 gene variation. If they do have a mutation in the APOL1 gene, you have a higher chance of your kidney disease coming back. Testing the APOL1 status of a person considering donating a kidney or of a deceased donor kidney is not currently required. However, studies have shown that transplanted kidneys from someone with the APOL1 gene have shorter survival. The decision to test for APOL1 status should be considered and discussed with your treatment team when making a decision about a transplant.
What steps can I take to prevent kidney disease if I learn I have APOL1 gene mutations?
It is estimated that if you test positive for mutations in both copies of the APOL1 gene, there is a 1 in 5 chance that you will go on to develop kidney disease.
If you have the APOL1 gene, you may be able to take part in clinical trials. This could provide an opportunity for researchers to develop and test safe treatments for APOL1-mediated kidney disease.
The participants in clinical trials should represent the diverse group of people who have the health problem being studied and will use the treatment out in the world. However, Black, Hispanic, Native American and Asian American people are often underrepresented in clinical trials. This means that compared to the number of people from these communities who are living with kidney disease, few participate in clinical trials. Learn more about why diversity in clinical trials is important and consider why you should take part in a clinical trial.
If you have the APOL1 gene mutation, your family members may also have the gene mutation. You may want to talk with your family members about speaking to their doctor about options for genetic testing.
There are currently no treatments available for APOL1-mediated kidney disease. However, there are steps you can take to protect your kidneys and promote general health.
Your doctor will work with you to create a plan to prevent or delay the progression of kidney disease, which may include:
- Visits with your doctor to check your blood levels and overall health
- A healthy eating plan. Your eating plan may involve limiting certain things, such as salt (sodium). Learn more about eating healthy.
- Taking all of your prescription medicines as your doctor tells you
- Being active at least 30 minutes a day on most days of the week
- Quitting smoking or using tobacco
APOL1-mediated kidney disease printable guide
Download and share our APOL1-mediated kidney disease information.
Listen to our APOL1 patient-video series
Emani talks about the signs and symptoms she experienced before genetic testing gave her the information she needed for a diagnosis.
Kevin talks about his journey to finding the right doctor for him, and his referral to a nephrologist that finally diagnosed his FSGS. As Kevin practiced becoming his own best advocate, he learned more about the positives of genetic testing to discover more about his health.
Therochelle recounts her emergency diagnosis of kidney injury, and the types of testing that eventually led her to a genetic test that provided answers. By asking questions and having conversations with her husband, doctors and friends Therochelle has become an advocate for kidney health and support pillar for others.
APOL1-mediated kidney disease: Sign up for more resources
Download this guide to connect with a genetic counselor. This one-stop tool can help you:
- Learn more about genetic testing for the APOL1 variant & benefits of genetic testing
- Getting the right counseling and education, as well as how to find a genetic counselor
- Prepare ahead of time before meeting a genetic counselor & questions you can ask
- Answers to frequently asked questions about genetic testing
Download this helpful genetic counselor guide
View our animated APOL1 explainer video and our webinar about why we should all care about APOL1.
Download the professional APOL1 webinar summary and guide
Use this guide alongside the APOL1-mediated kidney disease (AMKD):
Overview and implications for care webinar.
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