Scientists have identified an association between variants in the APOL1 gene and two measures of the severity of kidney disease in African Americans. In two separate studies, they found that APOL1 gene variants are associated with the rate of decline in kidney function in African Americans and also with the age at which individuals begin hemodialysis to treat kidney failure.
These studies build on information learned over the past few years about the contribution of genetic factors to the increased risk of kidney disease in this population. Previous studies have shown that African Americans with two copies of certain variants of the APOL1 gene are at increased risk of developing kidney disease. Indeed, these two variants, termed G1 and G2, are believed to explain much of the increased risk of non-diabetic kidney disease in this population.
One study examined biosamples from participants in the African American Study of Kidney Disease and Hypertension (AASK). The AASK study enrolled African American patients with mild kidney disease due to hypertension and found that treatment with an angiotensin converting enzyme inhibitor was better than two other drug options at slowing kidney disease progression. The investigators asked whether APOL1 and other gene variants were associated with an increased risk of worsening kidney disease in 700 AASK participants. They analyzed archived DNA samples and found that the presence of the G1 variant of the APOL1 gene was associated with a faster decline of kidney function compared to study participants without this variant.
Another study examined over 400 African Americans with kidney failure and asked whether the presence of 1 or 2 copies of either APOL1 variant was associated with a younger age at which the participants began hemodialysis, a therapy used to cleanse the blood of waste products and excess fluids and salts when the kidneys no longer function. The researchers found that African Americans with two copies of the G1 variant began hemodialysis at a significantly younger age (approximately 49 years old) than those with 1 copy of the variant (about 56 years old). People with 2 normal copies of the APOL1 gene began hemodialysis at around 62 years of age.
These findings have important implications for understanding the differences in kidney disease progression across different populations. They also suggest the APOL1 G1 variants may be a marker of an increased rate of kidney disease progression in African Americans. Therefore, early interventions to prevent progression of chronic kidney disease in this high-risk population may be of particular benefit.
Kanji Z, Powe CE, Wenger JB, et al. Genetic variation in APOL1 associates with younger age at hemodialysis initiation. J Am Soc Nephrol 22: 2091-2097, 2011.
Lipkowitz MS, Freedman BI, Langefeld CD, et al. Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int: 83: 114-120, 2013.