MedPath

APOL1 Genetic Testing in African Americans

Recruiting
Conditions
Genetic Predisposition
Chronic Kidney Diseases
Nephropathy
APOL1 Associated Kidney Disease
Disparities
Interventions
Genetic: Assessment of the frequency of APOL-1 renal risk variant in the black population, and evaluating their attitudes about genetic testing and APOL1 genotype via self-administered surveys
Registration Number
NCT05656261
Lead Sponsor
St. Louis University
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
600
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Adults of African or sub-Saharan ancestryAssessment of the frequency of APOL-1 renal risk variant in the black population, and evaluating their attitudes about genetic testing and APOL1 genotype via self-administered surveysThe study focuses on those who are at risk of having the APOL1 renal risk variants, which homozygous or compound heterozygous variants have been shown to lead to Chronic Kidney Disease in some of the population. Those who are found to have this mutations are of African or sub-Saharan ancestry. This study will include those aged 18-90 of this population.
Primary Outcome Measures
NameTimeMethod
Determine frequency of APOL1 renal risk variants in black population1 year

To assess the frequency and sociodemographic/clinical correlates of APOL1 renal risk variants in a local urban population of Black patients seen in Nephrology, Hypertension, Internal/Family Medicine clinics, or University Hospital.

Secondary Outcome Measures
NameTimeMethod
Determine frequency of first degree relatives of enrolled participants with APOL1 renal risk variants1 year

To assess the association and interaction between potential "second hits" such as environmental factors and comorbidities with APOL1 genotype on kidney function among Black patients and their families.

* To assess attitudes of patients and family members 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.

* To assess the interest of patients and family members in genetic counseling related to APOL1 genetic testing and kidney risk.

Trial Locations

Locations (1)

SSM Health Saint Louis University Hospital

🇺🇸

Saint Louis, Missouri, United States

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