Sickle cell trait in African-Americans associated with increased kidney disease risk, new research finds

Media contact: Tom Hughes, 984-974-1151,

Thursday, November 13, 2014

African-Americans carrying a genetic sickle cell trait face up to a two-fold risk increase for chronic kidney disease, according to a paper published today in the Journal of the American Medical Association.

The findings, which included data from nearly 16,000 people, may reverse current thinking on sickle cell trait – or SCT – a condition long considered benign. In practice, they may help flag kidney disease earlier, spur research into possible links between SCT and other common diseases, and ultimately improve public health.

Dr. Rakhi Naik, Johns Hopkins University assistant professor of medicine and the paper’s first author, said she wanted to investigate whether consequences exist to having SCT.

“It’s generally under-studied. There’s conflicting information and scant evidence out there about the implications of (sickle cell) trait,” she said.

“There have been national pushes for screening in many different contexts but really, not much is known about sickle cell trait. And as physicians, we don’t know specifically what to do with that screening information.”

People with SCT inherited a sickle cell gene copy from one parent. They usually don’t present disease symptoms. In contrast, those who suffer from sickle cell disease received gene copies from both parents.

About 1 in 12 African-Americans has SCT, as do about 300 million people worldwide. Though it’s most prevalent in people of African descent, sickle cell trait is also found in populations in the Middle East and India, Naik said.

Dr. James Wilson, University of Mississippi School of Medicine professor of physiology and a co-senior author on the paper, said the findings are scientifically impactful but shouldn’t cause public alarm.

“The overall message for people with sickle cell trait is that they still are healthy people. They are at a modestly increased risk for chronic kidney disease.”

Overall, African-Americans suffer chronic kidney disease at higher rates than whites and Asian-Americans. Further research might definitively show whether SCT is at play.

Paper co-first author Dr. Vimal Derebail, assistant professor of nephrology at the University of North Carolina School of Medicine, said the findings expand on previous preliminary studies of SCT group members had undertaken.

“Maybe these findings will help us gain a better understanding of the well-documented racial disparities in kidney disease,” said his colleague and co-senior author, Dr. Abhijit Kshirsagar, associate professor of nephrology at UNC.

In addition to Derebail and Kshirsagar, study co-authors from UNC are Nigel S. Key, MB, ChB, FRCP; Wayne Rosamond, PhD; and Nora Franceschini, MD.

Dr. Alex Reiner, a member of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center in Seattle and a professor of epidemiology at the University of Washington School of Public Health, co-led the project and is a co-senior author on the paper.

“These findings suggest that sickle cell trait, which is present in about 8 percent of African-Americans, appears to be one factor that contributes to the higher burden of kidney disease among that population. This study highlights the need for additional research into the health consequences of sickle cell trait.”

Reiner said the findings might have implications regarding screening or more closely monitoring kidney function in SCT carriers.

“Since screening for the sickle cell mutation is already widely performed in the U.S., these findings present additional public health and policy implications, including the role of genetic counseling, community awareness and education around genetic findings such as sickle cell trait,” he said.

In their study, the researchers analyzed data independently from African-American cohorts in five population studies. In each group they found SCT increased risk between 1.5 and 2 times. Altogether the analysis included data from 15,975 people.

“One of the convincing things is that the results were the same across all five studies,” Wilson said.

Dr. Adolfo Correa is University of Mississippi professor of medicine and pediatrics and interim director of the Jackson Heart Study, one of the five cohorts included in the investigation.

“These findings begin to open up a whole new horizon for research,” he said.

“Now that we appreciate that sickle cell trait can have an impact on kidney disease, we need to examine whether sickle cell trait may be associated with other chronic conditions.”

Future studies might evaluate possible associations between SCT and retinopathy, stroke and other conditions, said Correa, one of the paper’s co-authors.

Most immediately, he said, the researchers plan to look for SCT impact on the progression of chronic kidney disease to end stage renal disease.

While the findings hold potentially broad implications for genetic counseling, early detection of diseases and whittling of health disparities faced by African-Americans, further investigation will be necessary to yield specific recommendations.

“Right now it’s a little hard to say that we’re going to change anything clinically at this moment,” Naik said. “We found that trait is a risk factor for chronic kidney disease but we don’t know what the modifying environmental factors and other factors are. Not every single person with trait is going to develop kidney disease.”

Additionally, it’s yet unknown whether conventional methods of treating chronic kidney disease would reduce the risk specifically associated with SCT, Wilson said.

Naik said she hopes this and related research will ultimately build the knowledge base and treatment methods to intervene on SCT if necessary.

While no specific funding was allocated for the study, each of the five population studies included in the research – JHS, Atherosclerosis Risk in Communities Study (ARIC), Coronary Artery Risk Development in Young Adults Study (CARDIA), Multi-Ethnic Study of Atherosclerosis (MESA), Women’s Health Initiative (WHI) – received primary funding from the National Heart, Lung, and Blood Institute.