Recent breakthroughs in medical genetics have discovered that a portion of kidney failure affecting the Black community is mediated by coding variants in a gene called apolipoprotein L1 (APOL1) - and that genetic variants, not race - account for increased risk. For APOL1 genetic testing to be applied in a manner that improves patient care and outcomes, more information is needed regarding associations of genotype with clinical parameters related to kidney health. Further, understanding patient perceptions about knowledge of the results of APOL1 genetic testing, and how that impacts patient engagement with management of hypertension and other renal risk factors, is urgently needed.

• In a Phase 1 pilot study, we offered APOL1 genetic testing to Black patients seen in our Hypertension and Nephrology clinics at Saint Louis University, an academic medical center that serves the local urban community, and surveyed patients on attitudes and concerns about APOL1 genetic testing. 144 participants were enrolled in Phase 1.
• In the Phase 2 study, we will advance this important work in our community by offering participation to a broader patient base, including patients seen in Internal and Family Medicine clinics, SLU Hospital, as well as to first-degree relatives and spouses of SLUCare participants. This expansion seeks to advance understanding of environment-gene interactions, improve risk prediction, and target management of potentially modifiable risk factors.

Recent recognition of coding variants in the Apolipoprotein L1 (APOL1) gene as a strong risk factor for advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in African Americans (AAs) has marked one of the most impactful discoveries in kidney precision medicine. It is well-established that AAs have an increased risk of kidney failure, but it now appears that at least a portion of this risk disparity is genetically mediated by APOL1 renal risk variants (RRVs). Approximately 13% of Black Americans have APOL1 high-risk genotypes (2 copies of G1, G2, or compound heterozygotes [2 RRVs]) and are at higher risk for ESKD. Importantly, APOL1 high-risk genotypes are not deterministic for kidney disease. Rather, additional genetic and/or environmental "second hits" are likely required for disease initiation and progression. These "second hits" may include environmental factors and social determinants of health, as well as biologic factors.

Supported by the Mid-America Transplant Foundation, this study seeks to assess the frequency of APOL1 RRVs in local African American patients with hypertension and to assess their attitudes about APOL1 genetic testing and the potential impact of knowing one's APOL1 genotype on hypertension and renal risk factor management through self-administered surveys.

This study is open to Black patients seen in SLUCare Nephrology, Hypertension, Internal/Family Medicine clinics, or the University hospital, as well as to first-degree relatives and household family members (e.g. spouses) of enrolled participants or previously APOL1 genotyped patients of SSM Saint Louis University Hospital and SLUCare clinic. Family-based recruitment may help discriminate impacts of genetic risk from other potential shared biologic and non-biologic risk factors, and will also broaden the reach of the project in our community.

Inclusion Criteria:

• Ages 18-90
• Self-Identified as Black/African American. Race will be self-identified. Patients of African ancestry who identify as multi-racial are also eligible to participate.

Exclusion Criteria:

• Cognitively impaired/unable to provide consent
• Terminally ill
• Renal replacement therapy (RRT), e.g., (but not limited to) hemodialysis, peritoneal dialysis

• Black patients seen at Saint Louis University Internal Medicine, Family Medicine, Hypertension and Nephrology Clinics
• Family members on enrolled patients, including first-degree relatives and household family members (e.g. spouses). Up to 3 family members per enrolled patient may also be enrolled.
• Participation is also open to family members of SLUCare patients who have undergone APOL1 genotyping as part of clinical care (i.e., during evaluation of chronic kidney disease, including for kidney transplantation evaluation, or during living donor candidacy evaluation)