Paul Auer, assistant professor of biostatistics in the Joseph J. Zilber School of Public Health at the University of Wisconsin-Milwaukee, was one of the researchers involved in the study and a co-author of the paper.
Sickle cell trait is a condition in which a person has only one copy of the gene for sickle cell but does not have sickle cell disease (which requires two copies of this gene)
The findings 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, according to a JAMA news release.
The study is being released to coincide with the researchers’ presentation at Kidney Week 2014, the world’s premier nephrology meeting hosted by the American Society of Nephrology.
Dr. Rakhi Naik, Johns Hopkins University School of Medicine 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 but really, nothing has come of it. And as physicians, we don’t know specifically what to do with that screening information.”
People with SCT inherit a sickle cell gene copy from one parent, but usually don’t present disease symptoms. In contrast, those who suffer from sickle cell disease receive gene copies from both parents.
About 1 in 12 African-Americans has SCT. Though it’s most prevalent in people of African descent, sickle cell also developed independently in populations in the Middle East and India, Naik said.
Dr. James Wilson, University of Mississippi School of Medicine professor of physiology and biophysics 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, according to the news release.
Dr. Alex Reiner, a member of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center 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.”
“We have had anecdotal information that there was an association,” says Auer, “but this study provides the first statistically valid evidence for the link.
“This is an important finding for African-Americans,” he adds. Chronic kidney disease may stem from a variety of factors, but finding this link between sickle cell carriers and the development of the disease may help in prevention efforts for those at risk, according to Auer.
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 independently analyzed data from African-American cohorts in five population studies. In each group, they found SCT increased risk of kidney disease 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, University of Mississippi Medical Center professor of medicine and pediatrics and interim director of the Jackson Heart Study, one of the five cohorts included in the investigation, was co-author of the study. “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, there’s no reason not to think that something comparable may be going on with other organ systems.”
Future studies might seek associations between SCT and retinopathy, stroke, heart attacks, hypertension and other conditions, said Correa.
Most immediately, he said, the researchers plan to look for SCT impact on the progression from 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.
UWM CONTACT: Paul Auer, Cell: 206-890-2134.
As Wisconsin’s premier public urban institution, the University of Wisconsin-Milwaukee enjoys a growing national reputation for excellence in research, teaching and community engagement. On an operating budget of $680 million, it educates approximately 30,000 students and is an engine of innovation for Southeastern Wisconsin. The 104-acre main campus and satellite sites are located in the economic and cultural heart of the state. The university’s recent expansion includes new academic and research facilities and the creation of the only School of Freshwater Sciences in the United States and the Joseph J. Zilber School of Public Health.