New research, published in an upcoming issue of the Journal of the American Society of Nephrology, suggests that widespread screening for certain genetic variants in the black general population is not yet justified.

African Americans have an elevated risk for chronic kidney disease and kidney failure compared with European Americans. Studies have shown that much of this risk is due to genetic variations in a gene called apolipoprotein L1 (APOL1), which creates a protein that is a component of HDL, or good cholesterol. These variants arose tens of thousands of years ago in sub-Saharan Africa, and so are present in individuals who have recent sub-Saharan African ancestry. Approximately 5 million African Americans carry APOL1 risk variants; however, not all persons with such variants develop kidney disease.

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To getter a better sense of how APOL1 genetic risk variants affect kidney disease and other aspects of health over the long term, Morgan Grams, MD PhD (Johns Hopkins University) and her colleagues evaluated the prognosis and APOL1 status of participants in the Atherosclerosis Risk in Communities (ARIC) study. Among 15,140 ARIC participants followed from 1987–1989 to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. “Our study is a population-based cohort following participants over 25 years and thus well suited at assessing a fairly comprehensive set of outcomes among people with the high-risk genotype,” said Dr. Grams.

In analyses that adjusted for differences in demographics, black people had a higher risk for all assessed adverse health events: acute kidney injury, kidney failure, hypertension, diabetes, cardiovascular disease, hospitalization, and death; however, in analyses that also adjusted for comorbid conditions and socioeconomic status, black people had a higher risk for hypertension, diabetes, and kidney failure only. When considering only black people, the APOL1 high-risk variants were linked with a higher risk of kidney failure, but there was high variability in kidney function decline among those with and without the variants.

“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,” said Dr. Grams. “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.”

Study co-authors include Casey Rebholz, PhD; Yuan Chen, MS; Andreea Rawlings, MS; Michelle Estrella, MD MHS; Elizabeth Selvin, PhD; Lawrence Appel, MD; Adrienne Tin, PhD; and Josef Coresh, MD PhD.

Disclosures: The authors reported no financial disclosures. MG receives support from the National Institute of Diabetes and Digestive and Kidney Diseases (K08DK092287). CMR receives support from a National Heart, Lung, and Blood Institute training grant in Cardiovascular Epidemiology (T32 HL007024). AT receives support from a Renal Disease Epidemiology training grant from the National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007732). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts. The authors thank the staff and participants of the ARIC study for their important contributions.