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APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease
Study Questions:
What are the effects of apolipoprotein L1 (APOL1) risk variants on the progression of chronic kidney disease (CKD)?
Methods:
The authors examined the effects of APOL1 risk variants on the progression of CKD separately in the AASK (African American Study of Kidney Disease and Hypertension) and the CRIC (Chronic Renal Insufficiency Cohort) study. Patients in AASK were self-identified as black and had CKD attributed to hypertension; between 1995 and 2001, 693 were included in the current study after providing informed consent for collection of DNA and having adequate genotyping data. The authors reported the association between APOL1 risk status (defined by 0, 1, or 2 copies of the risk alleles) and the composite renal outcome (doubling of the serum creatinine level from baseline or incident end-stage renal disease). In the CRIC study, the primary exposure variables were racial ancestry (black or white) and APOL1 risk status (genotyped only in the black patients); patients were enrolled from 2003 to 2008 (and patients with diabetes were included). The primary outcomes were the rate of decline of kidney function and the composite of end-stage renal disease or a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline.
Results:
In the AASK study, the primary outcome occurred in 58.1% of those with high-risk APOL1 status (93 of 160 patients), compared to 36.6% in the APOL1 low risk status (hazard ratio, 1.88; P<0.001). The effect of APOL1 was not confounded by hypertension, and baseline proteinuria did not modify the effect of APOL1 on disease progression. Compared to white patients in the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcomes (in both diabetic and nondiabetic patients, p < 0.001 for all comparisons).
Conclusions:
There is a strong association between the presence of renal APOL1 high risk variants and disease progression. Nonetheless, the presence of APOL1 risk variants does not alone account for racial disparities in rates of progression of CKD.
Perspective:
Although little is known about the role of APOL1 in the kidney, a chromosomal region containing the gene encoding APOL1 has been implicated in the increased risk of black patients for CKD attributed to hypertension. In the present analysis of the AASK and CRIC studies, the authors provided convincing evidence that APOL1 high risk status is associated with disease progression. While these results help to elucidate the increased risk of end-stage renal disease among black patients (compared to white patients), there is still a need to understand other factors that may account for remaining racial disparities in disease progression of CKD. Future studies should also clarify our understanding of APOL1; as the authors acknowledge, there is a possibility that the adverse outcomes related to APOL1 high risk variants are related to their linkage with other causal variants or genes.
Keywords: Risk, European Continental Ancestry Group, Proteinuria, Creatinine, Renal Insufficiency, Kidney Diseases, Biomarkers, Cardiology, Glomerular Filtration Rate, Genotype, African Continental Ancestry Group, Hypertension, United States, Diabetes Mellitus, Disease Progression
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