Communities Inform APOL1 Genetic Testing Policy

Gathering African American perspectives nationwide on kidney disease risk.

Mistrust is a major barrier to genetic testing and preventive medicine in the African American community. “Mistrust of the health care system, research, and community-based screening always rears its head because of the historic experiences of African Americans,” said Ebele Umeukeje, M.D., assistant professor of medicine and nephrologist at Vanderbilt University Medical Center.

A controversial topic has been the recent discovery of high risk APOL1 variants that confer increased risk for chronic and end stage kidney disease and contribute to significant disparities in kidney disease among African Americans. Currently, not much is known about the mechanism by which APOL1 risk is conferred, whether preventive measures can reduce risk, or what other environmental exposures or comorbidities influence penetrance.

Umeukeje garnered African American perspectives on APOL1 testing through an evidence-based method of community deliberations. The results, published in the Journal of the American Society of Nephrology, will be connected with other epidemiologic studies to inform policy related to genetic testing.

“Why are you just now telling us?”

Certain APOL1 variants double a person’s risk of chronic kidney disease (CKD), and are associated with a seven- to ten-fold greater risk of non-diabetic end-stage kidney disease (ESKD). About 13 percent of African Americans have two high-risk alleles, but only one in five will go on to develop ESKD requiring dialysis. APOL1 variants may also contribute to loss of cadaveric kidney transplant over time.

“The APOL1 risk variant was discovered over eight years ago, and may be the most important factor contributing to racial and ethnic disparities in kidney disease,” Umeukeje said.

One community member shared concerns: “You’ve known about this for years. Why are you just now telling us about this?” As Umeukeje explained, “It’s currently not actionable. Even if we decide to do a genetic test, we still don’t know how to identify who will go on to develop disease.”

More Than a Focus Group

To deliberate risks and benefits of APOL1 testing, Umeukeje and a team of researchers turned to African American communities in Seattle, Washington; Jackson, Mississippi; and Nashville, Tennessee. The team included Kerri Cavanaugh, M.D., associate professor of medicine and co-director of the Vanderbilt Center for Effective Health Communication. Their goal was to reach consensus on issues related to testing to report back to policymakers in D.C.

“We used a public deliberation method, which is not often used in medical research. Qualitative studies tend to use focus groups or semi-structured interviews,” Umeukeje said.

A deliberation approach requires participants be demographically diverse and well-informed. The researchers enrolled men and women across age and economic brackets. All 39 participants received a two-page document summarizing what is known about APOL1, plus an interactive lecture. After overnight reflection, participants reconvened for large and small group deliberations. Surveys revealed conclusions on key issues.

Consensus For Transplants

“In the context of kidney transplant, we had consensus,” Umeukeje said. All participants agreed cadaveric kidneys should be tested for APOL1 variants. All but two participants also supported offering testing to living donors, but most (73 percent) opposed mandatory testing of living donors. Ninety percent opposed a policy that would prohibit those with APOL1 variants from donating a kidney.

Patients were circumspect when it came to routine patient care. Sixty-four percent supported offering APOL1 testing to all black patients, and support dwindled for focused testing of African Americans with specific risk factors, such as signs of CKD (10 percent supported).

Said one Nashville participant, “What difference does it make? If I take the test, it’s just going to be part of my record that I have this genetic disorder…nothing can be done about it.”

Connecting Data to Policy

“We can connect all these pieces together and provide information that will guide future policy.”

The community deliberations were one part of a larger National Human Genome Research Institute study. The researchers used the same deliberation approach to gather input from physicians, researchers, patient advocates and NIH representatives on APOL1 screening.

“We can connect all these pieces together and provide information that will guide future policy,” Umeukeje said. The results will also support physicians. “When the average physician has a patient who just tested positive for these high-risk variants, we need to make sure they have what they need to guide the patient.”