Sickle Cell Trait Linked with Greater Risk of Developing End-Stage Kidney Disease, Study Shows

Individuals with sickle cell trait (SCT), a common hemoglobin gene variant in African-Americans, have an increased risk of developing kidney disease, new research shows. These findings may have important implications in genetic counseling for individuals with SCT.

The study “Sickle Cell Trait and the Risk of ESRD in Blacks” appeared in the Journal of the American Society of Nephrology.

African-Americans show increased risk of developing end-stage renal disease (ESRD), the last stage (stage 5) of chronic kidney disease, which requires dialysis or a kidney transplant.

Individuals with SCT and hemoglobin C trait, another common hemoglobin gene variant in African-Americans, carry one copy of the variant. Unlike individuals with two copies, these individuals do not show symptoms of disease. In addition to the well-known APOL1 genetic high-risk, SCT and hemoglobin C trait are suggested to play a role in kidney disease in African-Americans. However, the association of these hemoglobin traits with ESRD was unknown.

The research team, led by Mary Cushman, MD, medical director of the Thrombosis/Hemostasis Program and professor at University of Vermont College of Medicine, performed a population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Their work evaluated 9,909 self-reported African-Americans who were 45 years or older, including 739 individuals with SCT and 243 with hemoglobin C trait. Median follow-up for ESRD was 6.5 years.

Researchers found that ESRD occurred in 5.4% of individuals with SCT, 2.5% of individuals with hemoglobin C trait and 2.6% of noncarriers.

Furthermore, the incidence rate for ESRD was 8.5 per 1,000 person-years for SCT and 4.0 per 1,000 person-years for non-carriers. Conversely, incidence for APOL1 high-risk genotypes was 6.6 per 1,000 person-years.

Unlike hemoglobin C trait, SCT strongly associated with development of ESRD in African Americans. The degree of risk of SCT for ESRD was similar to APOL1 high-risk genotypes.

“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have such as diabetes or high blood pressure,” Rakhi P. Naik, MD, the study’s corresponding author and assistant professor of medicine at Johns Hopkins University, said in a press release  “We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease specifically in individuals with sickle cell trait.”