Researchers aim to repurpose diabetes drug to treat SCD kidneys
UIC scientists get federal grant to test empagliflozin safety, effectiveness
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Researchers from the University of Illinois Chicago (UIC) have received $3.78 million in federal funding to evaluate whether a diabetes medication can slow kidney damage in people with sickle cell disease (SCD).
People with SCD face a higher likelihood of developing chronic kidney disease and often lose kidney function faster than people without the condition. Some patients progress to end-stage kidney disease, in which the kidney no longer functions as it should and life-sustaining treatments such as dialysis or kidney transplantation become necessary. Kidney failure is thought to contribute to the reduced life expectancy seen among people with SCD.
The five-year grant, from the National Institutes of Health’s National Heart, Lung and Blood Institute, will support studies in patients and mice evaluating empagliflozin, a drug that aims to protect the kidneys by increasing their ability to excrete sugar (glucose) into the urine.
The research will be led by Santosh Saraf, MD, UIC professor of hematology and oncology, and Anand Srivastava, MD, associate professor of nephrology.
“Once kidney disease develops, patients with sickle cell disease have a very rapid decline in kidney function,” Saraf said in a university press release. “We do not really understand why or how the kidneys are damaged, and there are currently no therapies approved that have been rigorously tested to look at how they might affect kidney function.”
Encouraging preliminary data on empagliflozin
Empagliflozin, sold as Jardiance, is approved to lower blood sugar in people with diabetes and to slow kidney damage in people with chronic kidney disease.
However, people with SCD have been excluded from clinical trials evaluating the drug, so it’s not known if it can also protect the kidneys in people with chronic kidney disease due to SCD.
Preliminary data from a small study at UIC showed some benefits from empagliflozin in three people with SCD and chronic kidney disease who also had diabetes.
“It was only three people, but in that small report we saw favorable outcomes, which gave us some foundation to look at this in a larger pilot of patients,” Srivastava said.
The new funding will allow researchers to confirm the findings in additional studies. The investigators will conduct parallel studies in SCD patients and in a mouse model of SCD to evaluate the safety and effects of empagliflozin on kidney function.
They will also use functional MRI to examine kidney oxygen levels, blood flow, and tissue scarring. This noninvasive imaging approach is particularly important, as kidney biopsies pose added risks for people with SCD.
“Our overarching goal is to demonstrate and hopefully show that empagliflozin is relatively safe and has similar shared benefits that we have seen in the chronic kidney disease population,” Srivastava added.
Saraf, who also directs the University of Illinois Health’s Adult Sickle Cell Center, said thousands of people with sickle cell disease live in the Chicago area alone, and treatment options remain extremely limited.
“The kidneys are perhaps the most common organ system that gets chronic damage,” he said. “Our team is really trying to understand how the kidneys are damaged and (how we) develop badly needed treatments to help protect the kidneys in people with sickle cell disease.”
