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APOL1, Sickle Cell Trait, and CKD in the Jackson Heart Study
Bessie A Young1,2,3,4, James G Wilson5, Alex Reiner6
1UW Office of Healthcare Equity, Justice, Equity, Diversity, and Inclusion Center for Transformational Research (UW JEDI-CTR), University of Washington, Seattle WA.
Insights
Two Apolipoprotein L1 (APOL1) risk variants increase chronic kidney disease (CKD) risk in African Americans. One APOL1 variant showed no increased CKD risk, and sickle cell trait did not modify APOL1
Area of Science:
- Nephrology
- Genetics
- Epidemiology
Background:
- Apolipoprotein L1 (APOL1) high-risk variants are linked to chronic kidney disease (CKD) in African Americans.
- The impact of a single APOL1 risk variant and the influence of sickle cell trait on CKD development are less understood.
Purpose of the Study:
- To investigate the association between APOL1 risk variants (one vs. two) and CKD outcomes in African Americans.
- To determine if sickle cell trait modifies the risk of CKD associated with APOL1 variants.
Main Methods:
- Utilized data from the Jackson Heart Study, a community-based longitudinal cohort of African Americans (n=5,306).
- Assessed APOL1 G1 and G2 genotypes and sickle cell trait.
- Employed multivariable regression models to analyze incident CKD, albuminuria, kidney function decline, and end-stage kidney disease (ESKD), adjusting for relevant covariates.
Main Results:
- Participants with two APOL1 risk variants showed significantly increased risks for albuminuria, ESKD, incident CKD, and both continuous and rapid kidney function decline compared to those with zero variants.
- Individuals with one APOL1 risk variant did not exhibit an increased risk for CKD outcomes.
- No significant interaction was found between APOL1 variants and sickle cell trait.
Conclusions:
- Two APOL1 risk alleles are associated with adverse kidney outcomes, including CKD, ESKD, and accelerated kidney function decline in African Americans.
- A single APOL1 risk allele does not appear to elevate CKD risk.
- Further research is needed to identify factors influencing kidney disease risk in individuals with high-risk APOL1 genotypes.
Rationale & Objective:
Apolipoprotein L1 (APOL1) high-risk variants are associated with an increased risk for chronic kidney disease (CKD) among African Americans. Less is known regarding the risk for the development of CKD and kidney failure (end-stage kidney disease [ESKD]) among African Americans with only 1 APOL1 risk variant or whether the risk is modified by sickle cell trait.
Study Design:
The Jackson Heart Study is a community-based longitudinal cohort study.
Setting & Participants:
Self-reported African Americans in the Jackson Heart Study (n = 5,306).
Exposures:
APOL1 G1 and G2 genotypes and sickle cell trait.
Outcomes:
Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2), albuminuria (urinary albumin-creatinine ratio ≥ 30 mg/g), continuous and rapid kidney function decline (≥30% decline), and incident ESKD.
Analytical Approach:
Multivariable linear and logistic regression, and Cox proportional hazards models adjusted for age, sex, hypertension, diabetes, ancestry informative markers, and sickle cell trait.
Results:
Of 2,300 participants, 41.3% had zero, 45.1% had 1, and 13.6% had 2 APOL1 risk variants. Sickle cell trait was present in 8.5%. Compared with participants with zero APOL1 risk variants, those with 2 alleles had an increased risk for incident albuminuria (adjusted HR [aHR], 1.88; 95% CI, 1.04 to 3.40), ESKD (aHR, 9.05; 95% CI, 1.79 to 45.85), incident CKD (aHR, 1.65; 95% CI, 1.06 to 2.57), continuous decline (β = -1.90; 95% CI, -3.35 to -0.45), and rapid kidney function decline (OR, 2.21; 95% CI, 1.22 to 4.00) after adjustment for sickle cell trait, with similar results after adjustment for ancestry informative markers. Having 1 APOL1 risk variant was not associated with CKD outcomes and there was no interaction of APOL1 with sickle cell trait.
Limitations:
Single-site recruitment of African American individuals with APOL1 and sickle cell trait.
Conclusions:
The presence of 1 APOL1 risk allele was not associated with increased risk for CKD outcomes, whereas 2 risk alleles were associated with incident albuminuria, CKD, ESKD, and rapid and continuous kidney function decline. Additional studies are needed to determine factors that might alter the risk for adverse kidney outcomes among individuals with high-risk APOL1 genotypes.
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