Community-Based Evaluation of APOL1 Genetic Testing in African Americans

Endstage renal disease (ESRD) or kidney failure affects over 500,000 persons in the United States and disproportionately affects racial and ethnic minority populations. Compared to whites, African Americans are 2-4 times more likely to develop ESRD, and represent 32% of the ESRD population, while only representing 13% of the US population. Two independent variants of the Apolipoprotein L1 (APOL1) gene, G1 and G2, have been associated with a 7 to 10-fold greater risk of developing non-diabetic ESRD in African Americans. Furthermore, people who inherit two risk variants (G1/G1, G2/G2 or G1/G2) are also more likely to develop ESRD at a younger age, and Individuals receiving donor kidneys from deceased individuals with two risk variants experience shorter kidney transplant survival. It is not known whether everyone with high- risk genotypes will develop ESRD; the exact mechanism of injury for APOL1-related risk or its relation to environmental exposures; or whether those with co-morbid conditions are more likely to develop ESRD. To address these uncertainties, research that includes assessment of APOL1 status will be needed. APOL1 testing may also be offered to African American patients to guide management of chronic kidney disease (CKD) or as part of prevention efforts aimed at reducing kidney disease, and has been proposed as part of kidney transplant protocols. Yet because of uncertainties regarding the clinical implications of APOL1 variants, testing could also generate confusion, anxiety or stigma. Multiple forms of evidence, including the views of community members, are needed to support responsible approaches to providing information about APOL1 status in research and clinical care. Research Goal: To determine African-American community views concerning the risks and benefits of returning information about APOL1 risk variants to research participants and testing for APOL1 risk variants in clinical care and renal transplant programs, and to promote inclusion of those views in policy discussions. To that end, the specific aims of the proposal are: Aim 1: Conduct key informant interviews with researchers, clinicians, community leaders, and African Americans with and without kidney disease, to determine their views about providing APOL1 results to research participants and utilizing APOL1 testing in clinical care, and renal transplant programs. Aim 2: Conduct three community-based deliberative groups to identify community preferences and priorities for responsible approaches to providing APOL1 results to research participants and utilizing APOL1 testing in clinical care and renal transplant programs. Aim 3: Convene a national meeting of stakeholders to review the current science of APOL1-related kidney disease, review findings of the deliberative groups, and develop guidance for policy-makers. The successful completion of this project will provide community-based guidance to researchers, clinicians and policy makers regarding the return of APOL1 results in research and the use of APOL1 testing in clinical care. PHS 398/2590 (Rev. 09/04, Reissued 4/2006)