Higher ESRD Risk in Blacks Not Due Solely to Genetic Variants

African Americans with and without a high-risk genotype experience similar kidney function decline.
African Americans with and without a high-risk genotype experience similar kidney function decline.

Although variants in the apoliprotein L1 gene (APOL1) have been linked with increased risks of kidney disease and failure, African Americans with the variants experience kidney function decline similar to that of blacks without the variants, a new study finds. 

"We found great variability in kidney function trajectory, such that most African Americans with the high-risk genotype experienced similar decline as African Americans with the low-risk genotype," lead researcher Morgan E. Grams, MD, from Johns Hopkins University in Baltimore, stated in a press release. "We did find pervasive racial disparities in adverse health outcomes not explained by the APOL1 risk variants, which suggests that interventions to improve health and health outcomes in African Americans are needed."

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Dr Grams and colleagues followed 15,140 participants ages 45–64 from the Atherosclerosis Risk in Communities study for 22.6 years, starting in 1987. The APOL1 gene contains code for a protein that is a component of high-density lipoprotein. The risk for variants of APOL1 was defined as high (2 or more alleles) or low (fewer than 2 alleles). Three quarters of participants were white with imputed APOL1 low-risk, 21.2% black with APOL low-risk, and 3.1% black with APOL1 high-risk.

Blacks had higher risks overall for new-onset hypertension, diabetes, and end stage renal disease (ESRD) after adjustment for co-existing conditions and income, according to results published in the Journal of the American Society of Nephrology

Among African Americans, having the APOL1 high-risk genotype was associated only with higher risk of ESRD after adjustment for covariates. High-risk status also was linked with faster decline in estimated glomerular filtration rate (eGFR), although the investigators observed variability. The annual decline was 1.5 mL/min/1.73m2 for whites compared with 2.1 for blacks with APOL1 low-risk and 2.3 for blacks with APOL1 high-risk. Most blacks had similar rates of kidney function decline regardless of their genetic variant status, when individuals with the fastest decline were excluded.

The findings generally agree with those from the Chronic Renal Insufficiency Cohort and African American Study of Kidney Disease and Hypertension studies, according to the investigators.

How APOL1 high-risk variants might affect kidney disease progression remains unclear. It is possible that “second hits” occur of genetic or environmental origin that compound risk.

“Given the variability in kidney function decline among persons with the APOL1 high-risk genotype, widespread screening of the black general population seems not yet justified,” Dr Grams and colleagues concluded. 

Sources

  1. Grams ME, Rebholz CM, Chen Y, Rawlings AM, Estrella MM, Selvin E, Appel LJ, Tin A, and Coresh J.Race, APOL1 Risk, and eGFR Decline in the General Population. J Am Soc Nephrol. doi: 10.1681/asn.2015070763.
  2. Blacks Face a Higher Risk of Kidney Failure Than Whites, Regardless of Genetics. [news release] American Society of Nephrology. March 10, 2016.
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