APOL1 Genetic Risk: How African Ancestry Increases Kidney Disease Chance

If you have recent African ancestry, your risk for kidney disease isn’t just about diet, blood pressure, or diabetes. A hidden genetic factor-APOL1-plays a major role in why kidney failure is so much more common in Black populations. This isn’t about race. It’s about ancestry, evolution, and biology.

What Is APOL1 and Why Does It Matter?

The APOL1 gene makes a protein that helps your body fight off a deadly parasite called Trypanosoma brucei rhodesiense-the cause of African sleeping sickness. Around 5,000 to 10,000 years ago, certain changes in this gene, called G1 and G2 variants, gave people in West Africa a survival advantage. Those with the variants were more likely to survive the parasite and pass the gene on.

Today, those same variants are linked to kidney damage. The irony? The very genes that saved lives from infection now increase the risk of kidney failure. These variants are found in about 30% of people from West African countries like Ghana and Nigeria. They spread through the African diaspora, meaning they’re common in African Americans, Afro-Caribbeans, and others with recent African roots.

But here’s the catch: you need two copies of the risky variant to be at high risk. That means G1/G1, G2/G2, or G1/G2. Only about 13% of African Americans carry this high-risk combination. Still, among those who develop non-diabetic kidney disease, nearly half have these variants. That’s why APOL1 explains up to 70% of the extra kidney disease risk seen in people of African descent compared to others.

How APOL1 Damages the Kidneys

The APOL1 protein normally attacks trypanosomes by punching holes in their membranes. But in kidney cells, the same trick turns harmful. The risk variants make the protein too aggressive. It starts damaging the filtering units of the kidney-the glomeruli-leading to scarring and loss of function.

This damage shows up as specific kidney diseases:

• Focal segmental glomerulosclerosis (FSGS)
• Collapsing glomerulopathy
• HIV-associated nephropathy (HIVAN)
• Arterionephrosclerosis (kidney damage from high blood pressure)

One study found that nearly half of all end-stage kidney disease cases in people of African ancestry with HIV were directly tied to APOL1. That’s staggering. And it’s not just HIV. Other triggers-like viral infections, obesity, or uncontrolled blood pressure-can push the system over the edge.

Most People With APOL1 Risk Don’t Get Sick

Here’s what many don’t tell you: having two risky APOL1 variants doesn’t mean you’ll definitely get kidney disease. In fact, about 80 to 85% of people with the high-risk genotype never develop serious kidney problems. That’s called incomplete penetrance.

Think of it like a loaded gun. The gene is the gun. But something else-like HIV, COVID-19, or chronic high blood pressure-pulls the trigger. That’s why doctors call these other factors “second hits.”

That’s also why some people live into their 70s with the variants and never know it. Others, especially younger adults, get hit hard after a viral infection or pregnancy. The timing is unpredictable.

Testing for APOL1: Who Should Get It?

Genetic testing for APOL1 became available in 2016. Today, companies like Invitae and Fulgent Genetics offer it for $250 to $450 without insurance. It’s a simple blood or saliva test.

Current guidelines recommend testing for:

• People of African ancestry with kidney disease, especially if it’s not caused by diabetes or high blood pressure
• Living kidney donors with African ancestry-because donating could put them at higher risk if they carry the variants
• People with a family history of early kidney failure

But here’s the problem: many doctors still don’t know how to interpret the results. A 2022 survey found that 78% of nephrologists felt undertrained in counseling patients about APOL1. Patients often misunderstand their risk-thinking a positive result means kidney failure is certain. It’s not. It means higher risk. Like smoking increases lung cancer risk, but not everyone who smokes gets cancer.

What to Do If You Have High-Risk APOL1

If you’re found to have high-risk APOL1, you’re not doomed. You’re just more vulnerable. And that means you can take action.

Experts recommend:

• Annual urine test for albumin (a sign of early kidney damage)
• Regular blood pressure checks-with a target under 130/80 mmHg
• Avoiding NSAIDs like ibuprofen or naproxen, which can stress the kidneys
• Controlling weight and avoiding smoking
• Getting vaccinated against viruses like HIV and COVID-19

One woman, Emani, found out she had the high-risk variants before any kidney damage. She started monitoring her urine and blood pressure yearly. Five years later, her kidney function is still normal. That’s the power of early awareness.

Why Race Doesn’t Explain This-Ancestry Does

You’ll hear people say “Black people have higher kidney disease rates.” That’s misleading. It’s not about skin color. It’s about genetic ancestry tied to West Africa.

These APOL1 variants are virtually absent in European, Asian, and Indigenous American populations. But they’re common in people whose ancestors came from Nigeria, Ghana, Senegal, or other parts of West Africa-even if they now live in the U.S., Canada, or the UK.

That’s why the medical community is moving away from race-based kidney estimates. In 2022, the American Medical Association officially discouraged using race to adjust kidney function tests (eGFR). Why? Because APOL1 shows that biology, not skin color, drives risk.

New Treatments Are on the Horizon

For decades, there was no treatment targeting APOL1 itself. But that’s changing.

Vertex Pharmaceuticals is developing a drug called VX-147 that blocks the harmful APOL1 protein. In a 2023 trial of 140 patients, it reduced protein in the urine by 37% in just 13 weeks. That’s a big deal-protein in urine is a key sign of kidney damage.

The NIH has invested over $125 million in APOL1 research since 2020. A new 10-year study called the APOL1 Observational Study is tracking 5,000 people with the high-risk variants to better understand who gets sick and why.

By 2035, experts believe APOL1-targeted therapies could reduce kidney failure disparities by 25 to 35%. But only if access is fair. Right now, only 12% of low- and middle-income countries can test for APOL1. That’s a justice issue.

Real Stories, Real Impact

One Reddit user, ‘BlackMedStudent,’ writes: “I have the high-risk genotype. I check my blood pressure every week. I get my urine tested every year. It’s stressful, but I’d rather know than wonder.”

Another person on the National Kidney Foundation’s forum said: “My doctor told me I have a 1 in 5 chance of kidney failure. The uncertainty is worse than a diagnosis.”

Those stories show the emotional weight of this knowledge. But they also show the power of control. Knowing your risk lets you act.

What’s Next?

By 2026, guidelines will likely recommend routine APOL1 screening for all adults of African ancestry with high blood pressure or early signs of kidney damage. By 2027, efforts will focus on making testing affordable and accessible everywhere-not just in wealthy countries.

For now, if you have African ancestry and have kidney issues-or a family history of them-ask your doctor about APOL1 testing. Don’t wait for symptoms. Don’t assume it’s just high blood pressure. This is a genetic risk, and it’s real.

The science is clear: APOL1 is one of the strongest genetic links to kidney disease ever found. And for the first time, we’re not just watching the problem-we’re building solutions.