UIC looks toward new treatment options for sickle cell patients with chronic kidney disease

Researchers from the University of Illinois Chicago have been awarded a five-year, $3.78 million grant from the National Heart, Lung and Blood Institute to study chronic kidney disease in people with sickle cell disease. Chronic kidney disease affects over half of those diagnosed with sickle cell disease and can lead to serious complications and early death.

Sickle cell disease is an inherited disorder caused by the improper functioning of hemoglobin, the protein that helps blood cells transport oxygen. Unlike typical red blood cells that easily bend and move, sickled cells are stiff and may get stuck in vessels, preventing oxygen from reaching organs and tissues and causing debilitating pain. About 100,000 people in the U.S. have sickle cell disease.

The study will evaluate the safety and effectiveness of empagliflozin, a sodium-glucose co-transporter 2 inhibitor, as a treatment. This medicine works by increasing the kidneys' ability to excrete glucose into the urine. The FDA has already approved this class of drugs for managing diabetes. This medicine has also been shown to protect the kidneys and slow the progression of chronic kidney disease, but so far, people with sickle cell disease have been excluded from these clinical trials.

"Once kidney disease develops, patients with sickle cell disease have a very rapid decline in kidney function," said Dr. Santosh Saraf, a professor of hematology and oncology and the project's co-principal investigator. "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."

The study will run parallel trials in patients and in a mouse model, and test the effects of empagliflozin on kidney function as well as functional magnetic resonance imaging (MRI) to assess kidney oxygenation, blood flow and scarring. This noninvasive imaging technique is important given the risks associated with kidney biopsies in patients with sickle cell disease.

"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," said Dr. Anand Srivastava, an associate professor of nephrology and co-principal investigator of the study.

Srivastava said their study will build on preliminary data from a very small study of patients with sickle cell disease who also had chronic kidney disease and 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," he said.

"There's roughly 3,000 to 4,000 people in Chicago with sickle cell disease alone," said Saraf, who also directs UI Health's Adult Sickle Cell Center. "There are very limited treatments to help people with sickle cell disease, and even more, recent cohorts have shown that the survival of people with sickle cell disease is 20 to 30 years shorter than that of people without sickle cell disease."

Organ damage is a common complication of the disease.

"The kidneys are perhaps the most common organ system that gets chronic damage," Saraf 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."

Additional UIC researchers include Suman Setty, Jin Han, Weiguo Li, Xiaohong Joe Zhou, Xu Zhang, Kim Silva, Armila Ruiz, Guohui Ren and Alana Aziz. Other contributors include Pottumarthi Prasad from NorthShore University Health System.