Professor of Medicine and Renal Division Chief at the University of Pennsylvania Perelman School of Medicine

Kirk Campbell, MD

April 28th, 2026, was the American Kidney Fund’s third annual APOL1-Mediated Kidney Disease (AMKD) Awareness Day, which urges clinicians to identify high-risk patients of African ancestry with unexplained kidney failure.

More than a decade after the discovery of APOL1 risk variants, translation into clinical care has been slower than many anticipated, with the field reaching an important milestone with the first proof-of-concept data for APOL1-targeted therapies.

As these treatments advance and longstanding questions around risk prediction, screening, and access remain unresolved, the focus is shifting toward how to translate this progress into equitable, real-world care.

In this Q&A, Kirk Campbell, MD, a nephrologist at Penn Medicine, discusses the evolving clinical landscape of APOL1-mediated kidney disease, the challenges that have slowed progress, and what must change to ensure emerging advances reach the patients most at risk.

HCPLive: We’ve known about APOL1’s role in kidney disease for over a decade. Why has translation into clinical practice been so slow and what has that delay meant for patients?

Campbell: It is a long time, but the fact that it took 13 years from the discovery of APOL1 kidney disease genetic association to the first proof-of-concept APOL1 inhibitor efficacy report should be celebrated. At the same time, the many uncertainties around disease pathogenesis have slowed translation in several ways. There are still no approved APOL1-specific therapies, no consensus on population screening, limited ability to predict who among carriers will progress and unresolved questions about “second hits,”

For patients carrying APOL1 high-risk variants, what does “risk” translate to in terms of real-world monitoring and follow-up today?

Approximately 14% of African Americans have the APOl1 high risk genotype. These two APOL1 risk variants confer roughly a 15%–20% lifetime chance of kidney disease, while also emphasizing that about 80% of people with two risk variants do not develop kidney disease

: With AMPLITUDE now in Phase 3 and Maze Therapeutics advancing a Phase 2 program, if one of these therapies succeeds, what needs to happen to ensure equitable access, particularly for patients with the highest genetic risk?

Campbell: Equitable access would require more than drug approval. It would require payer coverage for APOL1 testing, genetic counseling, urine albumin testing, nephrology referral, and the medication itself. It would also require that eligibility be based on genotype and clinical phenotype, not crude racial categories. Otherwise, we risk repeating the same inequities: patients with better insurance and academic-center access get tested and treated, while safety-net, rural, and historically underserved remain underdiagnosed. The highest-burden regions cannot be an afterthought. KDIGO notes that APOL1 kidney disease disproportionately affects communities with limited health-care and research infrastructure, and the report calls for community engagement, education, and clinical-trial participation strategies involving trusted community partners

: There’s ongoing debate about how to frame APOL1 risk, as a biological story, a population genetics story, or one rooted in structural inequities. Where do you land on that, and has your thinking evolved?

I would not choose only one frame. APOL1 is a biological mechanism, a population-genetics story, and a health-equity story at the same time. The biology matters because APOL1 variants can injure kidney cells and are now targetable. The population-genetics story matters because G1 and G2 variants are enriched in people with West and Central African ancestry and likely rose in frequency because of protection against certain trypanosomal infections. But the structural inequity story is just as important. Genetics may help explain susceptibility; it does not explain who gets screened, who has a primary care relationship, who sees a nephrologist early, who gets a transplant evaluation, who is offered genetic counseling, or who can afford a precision medicine.

: The KDIGO conference on APOL1 was held in Accra, Ghana. What does it mean for the field to be having these conversations on the African continent, and does that reflect a meaningful shift toward meeting patients where they are?

Campbell: It matters a lot. West Africa is central to our understanding of APOL1 kidney disease. KDIGO reports very high frequencies of APOL1 high-risk genotypes in West African populations, including up to 37% in Central Ghana and 50% in Southeastern Nigeria, and estimates that more than 100 million people in Sub-Saharan Africa may have two APOL1 high-risk alleles.

Holding the conference in Accra signals that the field is beginning to locate the conversation closer to the populations most affected, rather than treating African populations only as a source of retrospective genetic insight.

: If you had to leave clinicians with one practical implication about APOL1 today, what should it be?

Campbell: APOL1 testing is worth considering when the result can change follow-up, trial eligibility, transplant donor counseling, or future targeted-treatment decisions. But the test should come with counseling, and it should never replace a full kidney-disease workup. KDIGO explicitly says APOL1 testing can guide risk stratification and follow-up, but should not preclude diagnostic evaluation, including biopsy when clinically indicated.

Articles

APOL1-Mediated Kidney Disease (AMKD) awareness efforts underscore the lag between discovery of APOL1 risk variants and meaningful clinical translation, despite emerging proof-of-concept inhibitor data and late-stage trials. About 14% of African Americans carry a high-risk genotype, translating to an estimated 15%–20% lifetime kidney-disease risk, while most carriers never progress, highlighting persistent gaps in prediction and “second hit” biology. Equitable implementation will require coverage for testing, counseling, monitoring, referrals, and therapy, plus genotype-driven—not race-based—eligibility and stronger community-engaged infrastructure.

Campbell answers questions about the current research and clinical landscape of APOL1-mediated kidney disease. 