Sickle Cell Linked to Faster Kidney Function Decline in African-Americans, Study Shows

African-Americans with sickle cell trait and sickle cell disease have a significantly faster decline in kidney function than their unaffected peers with normal hemoglobin, a study suggests.

Men, people with diabetes, and those with good kidney function to start saw kidney function decline fastest, according to the study.

The findings support the need for further studies evaluating these potential risk factors and their underlying mechanisms, the researchers said.

The study, “Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study,” was published in the Journal of the American Society of Nephrology.

Sickle cell disease (SCD) is an inherited condition caused by a mutation in the HBB gene that affects the production of normal hemoglobin, the red blood cell molecule that carries and delivers oxygen to cells throughout the body. The altered hemoglobin, called hemoglobin S, causes oval-shaped red blood cells to take on a sickle shape.

People who inherit two abnormal copies of the HHB gene, one from each parent, develop SCD, while those with only one mutated HBB copy do not develop the disease, but instead, a condition called sickle cell trait (SCT).

SCT was previously thought to be harmless, but recent studies have shown that, like SCD, SCT contributes to a higher risk of chronic kidney disease. Despite the well-established association between hemoglobin S in SCT and SCD patients and chronic kidney disease, the effects of the abnormal hemoglobin in kidney function over time remain largely unknown.

Some 8% to 9% of all African-Americans have SCT, making them a high-risk population for kidney disease.

Researchers compared the annual change in the mean estimated glomerular filtration rate (eGFR) — a measure of kidney function — between African Americans with SCT and SCD and those with normal hemoglobin.

The team also evaluated potential risk factors for kidney function decline among people with SCT or SCD.

They used the Research Patient Data Registry data from January 2005 to June 2018 to identify black adults with SCT, SCD, or normal hemoglobin who had at least one year of follow-up and three eGFR values.

The final analysis included 1,251 people with SCT. Of those, 230 had SCD, and 8,729 had normal hemoglobin. Participants’ mean age was 36, and they were followed for a median of eight years.

Results showed that both SCT and SCD patients had a significantly faster decline in kidney function over time than unaffected people.

As expected, the decline was more pronounced in SCD patients than in people with SCT, “confirming that carrying one copy of the [mutated HBB gene] confers less harm to the kidneys compared with SCD,” the researchers wrote.

“Our findings suggest that black Americans with SCT lose nearly half an eGFR unit (ml/min per 1.73m2) more of kidney function every year than black Americans with a normal hemoglobin,” they wrote.

In people with SCT, lower levels of hemoglobin S were associated with faster eGFR decline. The researchers said that may be influenced by the presence of other, undetermined abnormalities in red blood cells.

“We identified several risk factors that need to be investigated in prospective studies to define best practices and interventions to attenuate eGFR decline and prevent incident CKD [chronic kidney disease] in black patients with SCT/SCD,” the researchers said.

Further studies are needed to better understand changes in hemoglobin S levels over time and how other hemoglobin forms and abnormalities may affect these levels in people with SCT, they said.