For people with recent African ancestry, kidney disease isn’t just about high blood pressure or diabetes. Behind many cases lies a hidden genetic factor: APOL1. This gene doesn’t cause disease on its own-but when two copies of certain variants are inherited, the risk of serious kidney damage jumps dramatically. And yet, most people-even many doctors-don’t know about it.
What Is APOL1 and Why Does It Matter?
APOL1 stands for apolipoprotein L1. It’s a gene that evolved in West and Central Africa thousands of years ago to protect against African sleeping sickness, a deadly parasite spread by tsetse flies. The variants called G1 and G2 made the protein better at killing the parasite. That advantage meant people with these variants were more likely to survive and pass them on. Today, about 30% of people with West African ancestry carry at least one of these variants.
But here’s the twist: having one copy is protective. Having two copies-whether G1/G1, G2/G2, or G1/G2-triggers something dangerous. The same protein that kills parasites starts damaging kidney cells. This leads to rare but aggressive forms of kidney disease like focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN), and collapsing glomerulopathy.
These variants are almost never found in people of European, Asian, or Indigenous American ancestry. That’s why kidney failure rates are 3 to 4 times higher in African Americans than in white Americans-and why APOL1 explains about 70% of that gap.
Who Has the High-Risk Genotype?
About 13% of African Americans carry two risk variants. That’s roughly 1 in 8 people. Among those who already have non-diabetic kidney disease, that number jumps to 50%. In people with HIV and kidney failure, nearly half of cases are linked to APOL1.
But here’s what most people don’t realize: having two bad copies doesn’t mean you’ll definitely get kidney disease. Only about 15-20% of people with high-risk genotypes ever develop serious kidney problems. That’s called incomplete penetrance. It means something else has to trigger it-what researchers call a “second hit.”
Common triggers include:
- HIV infection
- Systemic lupus
- Obesity
- Chronic high blood pressure
- Some viral infections
That’s why someone can have the high-risk genotype and live to 80 with perfect kidney function. Or why someone else develops kidney failure in their 30s after an HIV diagnosis. It’s not just genetics-it’s genetics plus environment.
How Is APOL1 Testing Done?
Testing for APOL1 variants is simple. It’s a blood or saliva test that looks for the G1 and G2 mutations. Results come back in about 1 to 2 weeks. The cost ranges from $250 to $450 without insurance, though some clinical studies cover it.
Testing is recommended in three main situations:
- If you have kidney disease and are of African ancestry
- If you’re considering being a living kidney donor and have African ancestry
- If you have a close family member with APOL1-related kidney disease
The American Society of Nephrology updated its guidelines in March 2023 to recommend annual urine tests (albumin-to-creatinine ratio) and strict blood pressure control (below 130/80) for people with high-risk genotypes-even if their kidneys seem fine now.
But here’s the problem: most doctors aren’t trained to talk about this. A 2022 survey found that 78% of nephrologists felt unprepared to explain APOL1 results to patients. Many still think kidney disease in Black patients is just about “hypertension” or “race”-not genetics.
Why Calling It a “Race-Based” Risk Is Dangerous
APOL1 is not about race. It’s about ancestry. Race is a social category. Ancestry is biology. You can have African ancestry without identifying as Black. You can identify as Black without recent African ancestry.
Using race to estimate kidney function (like the old race-adjusted eGFR formula) has caused real harm. It delayed diagnosis for many Black patients because their kidney function was artificially inflated. The American Medical Association banned that practice in 2022-partly because of APOL1 research.
Doctors who rely on race instead of genetics are missing the real cause. A patient with APOL1-related kidney disease might be told, “It’s just your race,” and never get tested. That’s dangerous. That’s why experts like Dr. Olugbenga Gbadegesin warn: “Don’t confuse race with ancestry.”
What You Can Do If You Have High-Risk APOL1
If you’ve been tested and have two risk variants, here’s what works:
- Check your urine every year for protein (albumin-to-creatinine ratio)
- Keep blood pressure under 130/80-medication may be needed
- Avoid NSAIDs like ibuprofen and naproxen-they stress the kidneys
- Manage weight and avoid smoking
- Get vaccinated against HIV and other infections
- See a nephrologist if you have signs of kidney damage
One patient, Emani, found out she had high-risk APOL1 before any damage occurred. She started monitoring her urine, lost 20 pounds, and got her blood pressure under control. Five years later, her kidney function is still normal.
Another person, a medical student with the same genotype, checks his urine weekly and gets blood pressure readings every month. “It’s anxiety,” he says. “But better anxiety than a transplant.”
What’s Coming Next: New Treatments
For decades, there was no treatment for APOL1 kidney disease. Now, that’s changing.
Vertex Pharmaceuticals tested a drug called VX-147 in a 140-patient trial published in October 2023. Results showed a 37% drop in proteinuria in just 13 weeks. That’s huge-protein in the urine is the earliest 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 high-risk genotypes to understand what triggers disease and how to stop it.
By 2035, experts estimate APOL1-targeted therapies could reduce kidney failure rates in African ancestry populations by 25-35%. But only if access is fair. Right now, only 12% of low- and middle-income countries can test for APOL1. That’s a global injustice.
What This Means for You
If you have African ancestry and you’ve been told you have kidney disease, ask: Could this be APOL1? If you’re healthy but have a family history of kidney failure, ask: Should I get tested?
APOL1 isn’t a death sentence. It’s a warning. And like any warning, it’s only useful if you act on it.
You can’t change your genes. But you can change how you live. You can monitor your health. You can ask the right questions. You can push for better care.
Knowledge isn’t just power here-it’s protection.
What does it mean to have two APOL1 risk variants?
Having two APOL1 risk variants (G1/G1, G2/G2, or G1/G2) means you carry a genetic profile that increases your risk for certain types of kidney disease, especially if another trigger like HIV, high blood pressure, or obesity is present. But most people with two variants never develop kidney disease-only about 15-20% do. It’s not a guarantee, just a higher chance.
Can I get tested for APOL1 if I don’t have kidney disease?
Yes. Testing is recommended if you have African ancestry and a close relative with unexplained kidney failure, or if you’re considering being a living kidney donor. Even without symptoms, knowing your status lets you take preventive steps like regular urine tests and blood pressure control.
Is APOL1 testing covered by insurance?
Coverage varies. Some insurance plans cover it if you have kidney disease or are a potential kidney donor. Without insurance, the cost is usually between $250 and $450. Some research studies offer free testing. Check with your nephrologist or a genetic counselor.
Does having APOL1 risk variants affect kidney transplants?
Yes. If you’re a living donor with two APOL1 risk variants, your own kidneys may be at higher risk for future damage. Guidelines now recommend testing potential donors of African ancestry. For recipients, having APOL1 variants doesn’t affect transplant success-but the donor’s APOL1 status can impact how long the new kidney lasts.
Are there any medications to treat APOL1 kidney disease?
Currently, no drugs are FDA-approved specifically for APOL1-related kidney disease. Standard treatments include ACE inhibitors or ARBs to reduce proteinuria and control blood pressure. But new drugs like VX-147 have shown strong results in early trials, with a 37% reduction in proteinuria after 13 weeks. These are expected to become available in the next few years.
Can I pass APOL1 risk variants to my children?
Yes. APOL1 risk variants are inherited in a recessive pattern. If you have two risk variants, each of your children will inherit one. They’ll only be at high risk if they inherit a second risk variant from the other parent. If only one parent has two variants, children will be carriers (one variant) and generally not at increased risk.
Why is APOL1 more common in people of African descent?
The G1 and G2 variants evolved in West and Central Africa 3,000-10,000 years ago to protect against African sleeping sickness. People with these variants were more likely to survive and have children. As a result, the variants became common in those populations and spread through the African diaspora. They’re rare in other groups because the evolutionary pressure didn’t exist there.
Yo, this is the kind of info that should be taught in high school bio class. I had no idea my grandma’s kidney issues were tied to this gene. My uncle died young from kidney failure and they just blamed his diet. Turns out it was genetics all along. Now I’m getting tested next month. If I’ve got the variants, I’m hitting the gym hard and ditching ibuprofen for good.