Combination of Genetic Markers Could Better Predict Kidney Disease in Sickle-cell Patients

Scientists have created a risk profile that uses three genetic markers to determine whether there is a high or low chance of a sickle-cell-anemia (SCA) patient developing kidney disease.

Preliminary results indicate that the combination does a better job of predicting kidney disease than markers used by themselves.

The study, “APOL1, Alpha Thalassemia, And BCL11A Variants As A Genetic Risk Profile For Progression Of Chronic Kidney Disease In Sickle Cell Anemia,” covers a combination of the gene-variant markers APOL1, alpha-thalassemia and BCL11A. The research was published in the journal Haematologica.

Chronic kidney disease (CKD) affects up to 58 percent of adults with SCA. It triples the risk of early death.

SCA affects 1 in 500 African Americans and 25 million people worldwide. It is caused by a mutation of the β-globin gene that triggers hemoglobin polymerization, or the combining of blood cells.

A number of genetic markers have been used to assess SCA-patient risk. Combining the markers into a risk profile may strengthen the predictive value over individual factors alone.

“We looked at the genetic factors already known to be associated with kidney disease or the degree of red blood cell hemolysis and examined the relationship they had with the condition in sickle cell patients,” Dr. Santosh Saraf, assistant professor of hematology and oncology at the University of Illinois at Chicago College of Medicine, said in a news release. “Our hypothesis was that a genetic risk profile that integrated APOL1, alpha-thalassemia and BCL11A would improve our ability to predict a patient’s risk for developing chronic kidney disease.”

Saraf said identifying patients who are at the greatest risk of developing CKD can help doctors develop individualized treatments.

Saraf’s team studied 262 adults being treated at the UI Health Sickle Cell Center between 2010 and 2016. They took blood samples and collected other data to analyze the genetic markers in the patients’ blood. All patients were followed to see which developed kidney disease.

The researchers discovered that using APOL1 G1/G2, α-thalassemia, and BCL11A rs1427407 together is a better predictor of a patient’s risk of developing kidney disease than a single marker.

Although the BCL11A marker is the subject of gene therapy trials for anemia and other red blood cell disorders, this is the first time it has been examined for its ability to predict kidney disease.

“The results of this study are encouraging,” Saraf said. “By understanding more about the genetic risk factors of kidney disease in sickle cell patients, we are one step closer to improving the length and quality of life for the millions of people worldwide living with sickle cell disease.”

“Using combinations of genes to better predict complications in sickle cell anemia is a new approach,” Dr. Victor Gordeuk, director of the sickle cell program at UIC, said. “The results of this study indicate that it is effective and probably can be improved on in the future to be an important part of our evaluation of patients.”