APOL1 Kidney Disease: Community, Trust, and Trial Participation

This episode focuses on APOL1-mediated kidney disease (APOL1 KD) in amalgamation as a scientific and a social inflection point.

Gillepsie recounts her experience on the Kidney Health Initiative (KHI) board, where a steering committee and workgroup were formed around 2020–2021 to build a roadmap for answering the needs of APOL1 KD. As sponsors were developing therapies, the insufficiency of traditional trial paradigms for this disease became apparent.

APOL1 KD has a disproportionate impact on Black Americans and individuals of African ancestry, communities that have been historically underrepresented, marginalized, and justifiably distrustful of medical research. Gillepsie explains that running an APOL1 trial requires “extra things” beyond protocol design, most importantly, engaging patients where they are and in ways that respect their lived experience. In the US, this has shown up as partnering with churches and faith leaders.1

From her experience, she shares a real-life example that illustrates how communication through trusted community members can transform participation in healthcare settings.

In a church with 103 congregants, after a preacher described a clinical trial for H. pylori reflux, 95 people consented to be screened.

APOL1 KD has therefore become a model for multi-stakeholder engagement, involving patients, faith leaders, clinicians, and sponsors.

Gillepsie outlines the 3 main objectives of the KHI APOL1 project:

1. Raise awareness of kidney disease and its disproportionate impact on Black Americans, including APOL1.
2. Increase screening for APOL1 variants and associated kidney disease.
3. Boost clinical trial participation so potential therapies can be robustly tested and reach patients.

She notes the extraordinary speed of progress for this disease. In 2011, high-risk variants APOL1 were discovered, and within about 15 years, phase 2 and 3 development programs are underway.

She contrasts this with IgA nephropathy (IgAN), first described in 1968, where it took > 50 years to get the first drug approved, and focal segmental glomerulosclerosis, first described a century ago, where appropriate endpoints are only now emerging.

APOL1 KD exemplifies how genotype-directed therapy plus thoughtful community engagement can compress timelines and bring precision medicine into nephrology.

Featured Experts

Barbara Gillespie, MD, Chief Medical and Strategy Officer of the International Society of Glomerular Disease and Adjunct Professor at the University of North Carolina

Tobias Huber, MD, President of the International Society of Glomerular Disease, Chair of the Center of Internal Medicine; Director of the III. Department of Medicine (Nephrology, Rheumatology, Endocrinology and Transplantation); and Director of the Hamburg Center for Kidney Health at the University Medical Center Hamburg-Eppendorf

Editors’ Note: Gillespie reports no relevant disclosures. Huber reports relevant disclosures with Boehringer Ingelheim, Novartis, Alexion, Pfizer, Retrophin-Travere, and Fresenius Medical Care.

References

1. Janeczko LL. Acute Kidney Failure Is More Prevalent Among African-Americans. HCPLive. Published November 8, 2013. Accessed March 6, 2026. https://www.hcplive.com/view/acute-kidney-failure-is-more-prevalent-among-african-americans

2. Campbell P. Inaxaplin Shows Promise for APOL1-Mediated FSGS in Phase 2a Trial. HCPLive. Published March 17, 2023. Accessed March 6, 2026. https://www.hcplive.com/view/inaxaplin-shows-promise-for-apol1-mediated-fsgs-in-phase-2a-trial