African Americans with the APOL1 gene variant experience faster progression of chronic kidney disease (CKD) and have a significantly increased risk of kidney failure, regardless of their diabetes status, finds a large study co-authored by Penn Medicine published this week in the New England Journal of Medicine.
The findings, published in conjunction with a presentation at the American Society of Nephrology annual meeting, come from the two largest prospective National Institutes of Health-funded study cohorts of nearly 5,000 individuals with kidney disease: the African-American Study of Kidney Disease and Hypertension (AASK) and the Chronic Renal Insufficiency Cohort (CRIC) study.
AdvertisementThose studies involve institutions from across the country, including the Perelman School of Medicine at the University of Pennsylvania, which houses the Scientific and Data Coordinating Center (SDCC) for the CRIC study, led by Harold I. Feldman, MD, MSCE who also chairs the study's national Steering Committee.
Dr. Feldman, director of Penn's Center for Clinical Epidemiology and Biostatistics (CCEB) and chair of its Department of Biostatistics and Epidemiology (DBE) and Amanda H. Anderson, PhD, MPH, assistant professor of Epidemiology in the DBE, are co-authors.
Past studies have found that APOL1 risk variants are associated with a 40 percent increased risk of CKD in African Americans compared to whites. Many, however, focused on people without diabetes. And for those that did focus on diabetes, the findings were inconsistent.
"This was a surprising finding for the group that helps answer another big piece of the puzzle," said Anderson. "In previous literature, there has been more of a definitive picture of blacks without diabetes, but here we demonstrated that APOL1 gene variants also play a role in the development of kidney failure in those with diabetes." Such information helps researchers better understand why African-Americans are four times more likely to develop kidney failure than whites, regardless of the cause of failure.
It also helps explain, in part, the faster progression toward kidney failure observed in blacks with CKD, she added.
In the AASK study, which enrolled only African Americans, kidney failure occurred in 58 percent of participants in the APOL1 risk group and 37 percent in the APOL1 non-risk group.
In the CRIC study, kidney function decline was greater among African Americans in the APOL1 risk group, but it was similar among African Americans in the APOL1 non-risk group and European Americans.
The findings provide direct evidence that African Americans with established CKD have a faster kidney function decline and increased rates of kidney failure compared with whites, and that APOL1 risk variants increase CKD progression in African Americans.
Senior authors include researchers from University of Maryland School of Medicine, Johns Hopkins Bloomberg School of Public and Georgetown University of School of Medicine.
"Knowing the role of these variants may lead to screening tests and new preventive measures for those at risk, such as earlier treatment," said Anderson.
The CRIC study, which started over 10 years ago, is a major national research effort—the Perelman School of Medicine leads a thirteen-institution consortium of academic medical centers — making fundamental insights into the epidemiology, management, and outcomes of CKD. It is supported under NIH grant U01DK060990.
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