APOL1 Genetic Risk: Understanding Kidney Disease in African Ancestry

• By Celeste Marwood
• 21 Nov, 2025
• 3 Comments

For people with recent African ancestry, kidney disease doesn’t just happen randomly. A hidden genetic factor - APOL1 - plays a major role in why rates of kidney failure are 3 to 4 times higher than in other populations. This isn’t about race. It’s about ancestry, evolution, and biology. And understanding it changes everything about how we prevent, test for, and treat kidney disease.

What Is APOL1, and Why Does It Matter?

APOL1 is a gene that makes a protein in your blood. Its original job? To protect you from African sleeping sickness. Thousands of years ago, in West and Central Africa, people who carried certain versions of this gene - called G1 and G2 - were more likely to survive infection by the Trypanosoma brucei parasite. Those who survived passed the gene on. Over generations, these variants became common in populations from that region.

But here’s the twist: the same change that saved lives from a deadly parasite now increases the risk of kidney damage. The APOL1 protein, in its mutated form, starts attacking the kidney’s filtering cells. It’s like a security system that’s too aggressive - it fights off invaders but ends up harming your own house.

These variants are almost never found in people of European, Asian, or Indigenous American ancestry. But in people with recent African ancestry - including African Americans, Afro-Caribbeans, and Black Africans - about 30% carry at least one copy. About 13% carry two copies. That’s the high-risk group.

How Do You Get High-Risk APOL1?

You don’t get it from your environment. You inherit it. Like eye color or blood type. But unlike most inherited diseases, APOL1 doesn’t follow a simple dominant pattern. You need two bad copies to be at high risk.

That means:

• G1/G1 (two copies of the G1 variant)
• G2/G2 (two copies of the G2 variant)
• G1/G2 (one of each - called compound heterozygous)

Only these combinations raise your risk significantly. If you have just one copy, you’re a carrier - you won’t develop APOL1-related kidney disease. But you can pass it on to your kids.

That’s why it’s called a recessive trait. And why most people with the high-risk genotype - around 80% - never develop kidney disease. Something else has to trigger it. That’s the "second hit." And that’s where things get complicated.

What Triggers Kidney Damage in High-Risk People?

Having two bad copies of APOL1 doesn’t mean you’ll get kidney failure. It means you’re sitting on a ticking clock. Something has to set it off.

Known triggers include:

• HIV infection - especially in the past, before antiviral treatments improved. HIV-associated nephropathy (HIVAN) was once common in Black patients with APOL1 risk variants. Today, it’s rarer, but still linked.
• High blood pressure - especially if it’s uncontrolled. Many people with APOL1 risk are told they have "hypertensive kidney disease," but the real driver may be the gene.
• Obesity and metabolic stress
• Other viral infections
• Chronic inflammation

One study found that nearly half of all end-stage kidney disease cases in Black patients with HIV were due to APOL1. Another found that among Black patients with non-diabetic kidney disease, about half had the high-risk genotype. That’s not coincidence. That’s causation.

What Kidney Diseases Are Linked to APOL1?

APOL1 doesn’t cause one single disease. It causes a group of rare but aggressive kidney conditions:

• Focal segmental glomerulosclerosis (FSGS) - scarring in the kidney’s filtering units. This is the most common.
• Collapsing glomerulopathy - a severe form of FSGS where the filters literally collapse. Often seen in HIV patients with APOL1 risk.
• Arterionephrosclerosis - kidney damage from high blood pressure, but worsened by APOL1.

These conditions progress faster than typical kidney disease. They respond poorly to standard treatments like steroids or ACE inhibitors. And they often lead to kidney failure before age 50.

Why Was This Missed for So Long?

For decades, doctors assumed kidney disease in Black patients was mostly due to high blood pressure or diabetes. Many were told their kidneys were failing because they were "Black." That’s not just wrong - it’s harmful.

Doctors used race-based formulas to estimate kidney function (eGFR). These formulas automatically adjusted results upward for Black patients, assuming they had more muscle mass. But that masked early kidney damage. Many people with APOL1 risk were told their kidneys were fine - when they weren’t.

In 2022, the American Medical Association officially recommended stopping race-based eGFR adjustments. It was a direct result of APOL1 research. You don’t need to guess someone’s race to understand their kidney risk. You just need to test their genes.

Who Should Get Tested for APOL1?

Testing isn’t for everyone. It’s targeted.

Current guidelines from the American Society of Nephrology (2023) recommend testing for:

• People of recent African ancestry with unexplained kidney disease - especially if it’s not caused by diabetes or high blood pressure.
• People with a family history of early kidney failure.
• Living kidney donors of African ancestry - because if they have high-risk APOL1, donating could put their own kidneys at risk.

The test is simple: a blood or saliva sample. Results come back in 7 to 14 days. Cost ranges from $250 to $450 without insurance. Some labs offer financial aid.

But here’s the catch: many doctors still don’t know how to interpret the results. A 2022 survey found that 78% of nephrologists felt undertrained in APOL1 counseling. Patients often walk away thinking they’re doomed. They’re not.

What Does a Positive Result Really Mean?

Let’s be clear: having two APOL1 risk variants doesn’t mean you’ll get kidney disease. It means your risk is higher - maybe 1 in 5 over your lifetime. That’s not 100%. That’s not a death sentence.

Most people with high-risk APOL1 live normal lives. Their kidneys stay healthy. But they need to be vigilant.

Doctors now recommend:

• Annual urine test for albumin (a sign of early kidney damage)
• Regular blood pressure checks - target under 130/80
• Avoiding NSAIDs like ibuprofen (they stress the kidneys)
• Controlling weight and avoiding smoking
• Getting vaccinated against HIV and other viruses

One patient, Emani, found out she had APOL1 risk before any damage occurred. She started monitoring, changed her diet, and stayed active. Five years later, her kidney function is normal. That’s the power of early awareness.

What’s Next? New Treatments on the Horizon

For years, there was nothing to do but wait and monitor. But that’s changing.

Vertex Pharmaceuticals, a major biotech company, has spent over $1.5 billion developing drugs that block the harmful APOL1 protein. Their drug, VX-147, showed a 37% reduction in proteinuria (protein in the urine) in a 2023 trial. That’s a big deal - proteinuria is a sign of kidney damage.

The NIH has launched a 10-year study tracking 5,000 people with high-risk APOL1. They’re trying to predict who will develop disease - and why. That could lead to personalized prevention plans.

And the global market for APOL1 testing is expected to nearly double by 2027. But access remains unequal. Only 12% of low- and middle-income countries offer testing. That’s a moral crisis. This isn’t just a science issue. It’s a justice issue.

Don’t Confuse Ancestry With Race

One of the most important lessons from APOL1 research is this: genetics is not race.

APOL1 risk variants are tied to West African ancestry. Not to skin color. Not to culture. Not to identity. But for years, medicine used race as a shortcut. That led to misdiagnosis, delayed care, and even denial of transplants.

As Dr. Olugbenga Gbadegesin says: "We must be careful not to conflate social constructs of race with genetic ancestry."

Testing for APOL1 removes the guesswork. It replaces stereotypes with science. And that’s progress.

What Can You Do If You’re at Risk?

If you’re of African ancestry and have kidney disease - or a family history of it - ask your doctor about APOL1 testing. Don’t wait until your kidneys are failing.

If you’re healthy but know you carry the risk:

• Get your urine tested every year.
• Keep your blood pressure under control.
• Don’t smoke. Don’t use NSAIDs long-term.
• Stay active. Eat less processed food.
• Find a nephrologist who understands APOL1 - not everyone does.

If you’re considering donating a kidney and have African ancestry - get tested before you donate. Your kidney might be at risk too.

Knowledge isn’t just power. It’s protection.