Just one sickle cell gene may raise kidney disease risk

"Finding that (having one sickle cell gene) can influence kidney disease is another piece of the puzzle to explaining the higher risk of chronic kidney disease in African-Americans," says Rakhi P. Naik. (Credit: Amrit/Flickr)

Inheriting the sickle cell gene from just one parent won’t trigger the painful illness, but it may elevate the risk of chronic kidney disease.

The findings, published in the Journal of the American Medical Association, may help explain why African-Americans—who account for the vast majority of Americans with either one or two sickle cell genes—suffer from chronic kidney disease more than white people, researchers say.


“Finding that (having one sickle cell gene) can influence kidney disease is another piece of the puzzle to explaining the higher risk of chronic kidney disease in African-Americans,” says Rakhi P. Naik, assistant professor of adult hematology at Johns Hopkins University School of Medicine and one of the study’s leaders.

Full-blown sickle cell disease causes red blood cells to “sickle” or bend, creating anemia and often extremely painful sickling “crises,” when the misshapen blood cells become lodged in small blood vessels.

Having sickle cell trait, or SCT, means that a person inherited the sickle cell gene from one parent, but does not have the two copies—one each from the mother and father—needed to cause sickle cell disease.

About 8 to 10 percent of African-Americans have SCT. Other racial and ethnic groups also carry the gene mutation, but to far lesser extents.

Malaria link

The mutated gene is thought to have developed in parts of the world where malaria is endemic, as it offers some protection against that disease. Researchers have begun to recognize a host of problems that may accompany SCT, ranging from increased risk of blood clots to sudden death.

Because blood in the urine and kidney vessel damage had previously been linked to SCT, researchers investigated whether SCT might also play a role in chronic kidney disease.

They used data from five large studies that followed populations of adults over time. Although the purpose of these studies was to better understand risk factors for cardiovascular disease, they also collected other useful health data, including patients’ kidney function and genetic information.

The researchers carved out information on 15,975 self-identified African-American participants, 1,248 with SCT and the rest non-carriers of the sickle cell gene. They looked specifically at how many in each group had developed chronic kidney disease or other markers of impaired kidney function, including poor ability to filter blood through the kidneys and the presence of protein in urine.

The incidence of chronic kidney disease was about 20.7 percent in those with SCT but only 13.7 percent of those without it. SCT carriers—who can pass the gene on to offspring—were also more likely to have impaired ability to filter blood through the kidneys and to have protein in their urine.

Localized sickling

The researchers hypothesize that although blood cells are less likely to sickle—or warp into a sickle shape—as severely or frequently in individuals with just one sickle cell gene, they still experience infrequent and localized sickling.

That might affect certain organs more than others, clogging blood vessels and restricting oxygen to these areas. The mild sickling may be enough to eventually damage kidneys, leading to chronic kidney disease and other kidney problems.

Though a separate genetic problem has recently been linked to increased chronic kidney disease risk, Naik says, it only explains part of the risk in African-Americans, and it cannot solely account for the high disparity of chronic kidney disease between African-Americans and whites.

“These findings may have implications for more closely monitoring kidney function in SCT carriers,” says Alexander P. Reiner, an epidemiologist at University of Washington and coauthor of the study.

Other study coauthors are from University of North Carolina, University of Mississippi Medical Center, and Fred Hutchinson Cancer Research Center.

Source: Johns Hopkins University