Abstract: FR-PO312
Sickle Cell Trait, APOL1 Renal Risk Variants, and Kidney Outcomes in the Million Veteran Program
Session Information
- Genetic Diseases: Models, Mechanisms, Treatments
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Thompson, Trevor, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Yu, Zhihong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Huffman, Jennifer E., VA Boston Healthcare System, Boston, Massachusetts, United States
- Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Gaziano, J. Michael, VA Boston Healthcare System, Boston, Massachusetts, United States
- Wilson, Peter W., Atlanta VA Medical Center, Atlanta, Georgia, United States
- Siew, Edward D., VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States
- Susztak, Katalin, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Bick, Alexander, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hung, Adriana, VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States
Group or Team Name
- Million Veteran Program
Background
Individuals of African ancestry, have a 4-fold increased risk of progression to End Stage Renal Disease (ESRD). Apolipoprotein 1 high risk variants (APOL1 HR) & Sickle Cell Trait (SCT), also denoted as the rs334 mutation, have been associated with greater ESRD risk. Both mutations arise in the same regions of West Africa due to positive evolutionary selection. Our previous GWAS in African American and Latinx populations showed that both the rs334 mutation in the HBB gene and APOL1 high risk variants were associated with lower GFR. It is not known if the association described for SCT and ESRD varies by APOL1 risk status.
Methods
We conducted a retrospective cohort study including 109,047 participants with African ancestry enrolled in the Million Veteran Program. We excluded patients with preexisting ESRD or Sickle Cell Disease. The primary exposure was APOL1 high risk variants (RV) (G1 and/or G2) and/or SCT, defined by heterozygosity at the HBB gene for the rs334 mutation. Our primary outcome was a 40% decline in eGFR or reaching ESRD. Patients were followed to an outcome, death, or last day of follow up. Multivariable Cox regression was used for the comparison.
Results
Overall, the median age was 59 years [IQR 51,66], 86.2% were male, 33% had diabetes (DM) and 66% had hypertension (HTN). 5,285 (4.85%) experienced an eGFR decline of 40% and 1,796 experienced incident ESRD. Cox regression results are presented in Table 1.
Conclusion
In patients without diabetes the APOL1 HR genotypes and SCT had the largest risk of progression. SCT did not confer increased risk of progression to ESRD for G0/G0 individuals. In diabetic patients with SCT and one high risk APOL1 variant, there was an increased risk of renal disease progression to the clinical outcomes described above. Understanding the interaction of DM and SCT in the risk of CKD progression deserves further investigation.
Funding
- Veterans Affairs Support