Pharmacy researcher receives $1.6 million to study treatment of deadly kidney injury

The National Institute of Diabetes and Digestive and Kidney Diseases has awarded a five-year, $1.6 million grant to Liwen Lai, PhD, a research professor at the University of Arizona College of Pharmacy, to study a novel agent for treating acute kidney injury.

Acute kidney injury is a serious condition with a mortality rate of 50 percent. It is estimated to affect more than half a million people per year in the U.S.

“Acute kidney injury currently affects approximately 5 percent of all hospitalized patients and about 30 percent of critically ill patients in intensive care units,” says Lai. “Unfortunately, to date the treatment for acute kidney injury has been mainly supportive. We often have to put patients who develop acute kidney injury on dialysis. There’s not a specific drug that can cure the condition. All clinical trials of pharmacological interventions have been unsuccessful.”

Acute kidney injury is caused by a number of conditions, including lack of blood supply to the kidney, septicemia (bacteria in the blood), and toxins to the kidney such as certain antibiotics, chemotherapy agents, anti-rejection agents, non-steroidal anti-inflammatory drugs and contrast agents for CT scans.

Due at least in part to the introduction of new drugs, increase in organ transplantations, and development of drug-resistant bacteria, the incidence of acute kidney injury has increased steadily over the last 10 years.

Researchers have long known that inflammation is the process which leads to the destruction of kidney cells during acute kidney injury, and that inflammation is initiated by a group of blood cells called T cells.

Among T cells, there is a unique group called regulatory T cells, or Tregs. Tregs are powerful cells which suppress all kinds of inflammatory cells, including T cells. During

acute kidney injury, there are few Tregs in the kidney. Lai’s team identified a particular drug, a derivative of sphingosine, which attracted Tregs to the kidney and effectively reduced the damage from acute kidney injury.

The discovery by Lai’s team that Tregs can be recruited by a drug to control tissue damage has tremendous application in health care.

“I’m very excited about this finding,” says Lai. “We need to study how the drug recruits Tregs and what the underlying mechanisms are. The NIH grant will allow us to do that.”

The results of Lai’s studies will provide the foundation for developing the Treg-recruiting agent into a first-in-class drug for some types of acute kidney injury and possibly many other inflammatory diseases, such as Type 1 diabetes and arthritis.

Lai’s collaborators include Howard Lien, MD, PhD, nephrologist and professor emeritus of medicine at the ArizonaHealthSciencesCenter, and Serrine Lau, PhD, professor at the UA College of Pharmacy and director of the college’s SouthwestEnvironmentalHealthSciencesCenter.