Approximately 13% of African American individuals have two copies of variants of the gene encoding apolipoprotein L1 (APOL1), placing them at risk of developing APOL1 kidney disease (1). Yet, few people know they have these variants or the risks they pose to their health.
These APOL1 risk variants are associated with faster kidney disease progression and are more common among individuals with focal segmental glomerulosclerosis, hypertension-associated kidney disease, HIV-associated kidney disease, and lupus nephritis. Lack of awareness may be contributing to disproportionately high rates of kidney diseases and progression to dialysis among African Americans in the United States, who account for 13% of the population but 16% of those with chronic kidney disease and 35% of those on dialysis, said Susanne B. Nicholas, MD, MPH, PhD, a professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “If we aren't able to get these patients with APOL1 risk variants tested early, which allows them to get treated when treatments are available, the consequences are a more rapid progression of their kidney disease to kidney failure, as well as overall poor clinical outcomes,” Nicholas said.
To prevent such poor outcomes, Nicholas is participating in a Kidney Health Initiative steering committee that is creating a roadmap to raise APOL1 kidney disease awareness, increase testing for these disease variants, boost participation of at-risk individuals in clinical trials, and reduce barriers to clinical trial participation for individuals in affected communities (2). To achieve this, the steering committee has brought together patient advocates, clinical researchers, pharmaceutical companies, and the US Food & Drug Administration to share their perspectives. “The roadmap will allow us to see where to begin, where we want to end, and how we can maneuver through [barriers] to get to the finish line,” said steering committee member Patrick Gee, Sr., PhD, a patient advocate and chair of the Kidney Health Initiative's Patient and Family Partnership Council.
Raising awareness
Many people in African American communities, particularly with low income or in rural communities, may be unaware of the threat of kidney risks associated with specific APOL1 variants. In fact, 8 of 10 people with kidney diseases do not know they have kidney diseases until they are diagnosed with kidney failure, said Opeyemi Olabisi, MD, PhD, assistant professor of medicine at Duke University School of Medicine (Durham, NC), who is advising the steering committee on the roadmap. “Kidney disease[s do] not announce [themselves] early,” Olabisi said. Instead, patients do not discover the disease until they may have lost 80% of their kidney function and begin experiencing symptoms like leg swelling.
Gee said people with kidney diseases also want to know why they have them, and many African American individuals may not find out they have an APOL1 kidney disease variant until a late stage of the disease. “They find out somewhere down the road, [the disease] was caused by APOL1, and they feel like they have been deceived,” Gee said.
That can further fuel mistrust in the medical community among African American individuals who are aware of historical mistreatment of the population in clinical research, such as the US Public Health Service's Syphilis Study at Tuskegee (3) or the use of Henrietta Lack's cervical cancer cells for research without consent (4), noted Olabisi. Lack of trust and structural barriers, such as the unavailability of transportation to clinical trial sites or less time to participate because of employment obligations, have led to low participation in clinical trials among African American individuals, he said. African American participants comprise <10% of clinical trial participants despite being disproportionately affected by kidney diseases, according to a publication co-authored by Nicholas on behalf of the Clinical Care & Innovation Workgroup of the ASN Health Care Justice Committee (5). The committee, of which Nicholas is a member, recommends that kidney disease clinical trials increase the number of African American participants to 35% to reflect the burden of kidney diseases. Committee members have created a scorecard to help clinical trials meet that goal.
Raising awareness of APOL1 kidney disease and its impact on African American communities can help empower individuals at risk and encourage more people to participate in clinical research. “People will be more willing to come forward because they understand that this does not just impact them, but it impacts family members, friends, and everybody in their community,” Gee said. “This roadmap has the potential to break down institutional biases and systemic roadblocks that have been in place for decades.”
Community engagement
The initiative is already helping to support community engagement and stakeholder partnerships. For example, through the initiative, Olabisi connected with representatives from Labcorp, who allow him to use a mobile clinic for his community engagement and clinical trial enrollment efforts. Olabisi and his team took the mobile clinic to the General Baptist State Convention of North Carolina in Wilmington. They used it to screen 60 participating church elders and leaders for APOL1 risk variants and protein in their urine. “We returned the results to them for free,” Olabisi said. “We were able to identify some people with high-risk APOL1 and some people who did not know they had protein in their urine.”
The participants are also given the information that they can share with their physicians and are alerted about ongoing clinical trials enrolling patients, including Olabisi's Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease (JUSTICE) trial (6). “We can engage the community productively,” he said. “It helps to bridge some of those historical, structural barriers that prevent African Americans from participating in research.”
Olabisi and his team have also collaborated with The River Church in Durham, NC. Bishop Ronald L. Godbee invited the group to a Sunday service to share information about APOL1 kidney disease and later held a screening event at the church during a Tuesday Bible study. Bishop Godbee and his wife volunteered to be the first people screened, and 80 individuals participated in that screening event, including some who have registered to participate in the JUSTICE trial. “When we meet people where they are, and we provide information that is accessible, African Americans are just as willing to participate in clinical trials as any other group,” Olabisi said.
Resource mapping
In addition to connecting stakeholders, the steering committee is building an online, interactive roadmap and a print version that should be available in August 2023. The roadmap will bring together existing resources for physicians, patients, researchers, drug makers, and other stakeholders. “We are not going to reinvent the wheel because there is a lot of information already out there,” Nicholas said. “The steering committee wants to engage more physicians in sharing information about APOL1 kidney disease with their colleagues and patients,” Nicholas continued. “Physicians can spread the word and recommend genetic testing for at-risk patients,” she said. “They can also become more knowledgeable about interpreting the testing and know which patients they should refer for genetic counseling.”
There will also be resources to help encourage more community engagement efforts like those of Olabisi's and information crafted by patient advocates like Gee for individuals with APOL1 kidney disease and those at risk.
“We would like patients to understand their risk factors for developing APOL1 kidney disease and to become empowered to incorporate disease-prevention strategies within their lifestyle, to seek out genetic testing, and to get actively involved in clinical trials, which is very, very important,” Nicholas said.
Participation and collaboration among all stakeholders are essential to developing new prevention and treatment strategies for patients with APOL1. “Our ultimate goal, through our trial and trials like it, will be to come up with treatments that prevent [kidney function] from being drained down to zero,” Gee said. “Can we stop the disease that APOL1 causes in the kidney?”
References
- 1.
Yusuf AA, et al. Kidney disease and APOL1. Hum Mol Genet 2021; 30:R129–R137. doi: 10.1093/hmg/ddab024
- 2.
ASN Steering Committee Workgroup Members. Kidney Health Initiative. Current project. Roadmap to increase disease awareness and clinical trial participation of people carrying high-risk genetic variants of APOL1-associated nephropathy. Accessed March 7, 2023. https://khi.asn-online.org/projects/project.aspx?ID=91
- 3. ↑
US Centers for Disease Control and Prevention. The U.S. Public Health Service Syphilis Study at Tuskegee. https://www.cdc.gov/tuskegee/timeline.htm
- 4. ↑
Henrietta Lacks: Science must right a historical wrong. Nature 2020; 585:7. doi: 10.1038/d41586-020-02494-z
- 5. ↑
Nicholas SB, Cervantes L; Clinical Care & Innovation Workgroup of the American Society of Nephrology Health Care Justice Committee. Health care equity and justice scorecard to increase diversity in clinical trial recruitment and retention. J Am Soc Nephrol 2022; 33:1652–1655. doi: 10.1681/ASN.2022040427
- 6. ↑
Clinicaltrials.gov. Janus Kinase-STAT Inhibition to Reduce APOL1 Associated Kidney Disease (JUSTICE). ClinicalTrials.gov Identifier: NCT05237388
