Can a Diabetes Drug Prevent Kidney Injury After Trauma? USU Research Explores Canagliflozin

Uniformed Services University research explores the potential of canagliflozin, a diabetes medication, to prevent acute kidney injury in trauma patients.

Members of 47th Task Force Medical demonstrate the Resuscitative Endovascular Occlusion of

the Aorta trainer.  REBOA is a valuable endovascular strategy for managing uncontrolled

hemorrhage and temporary blood flow loss, helping to improve perfusion and reduce organ

damage in both military and civilian medical settings.  (U.S. Army Photo taken by Sgt. Dennis

Glass)

March 20, 2025 by Vivian Mason

A desire to improve military and civilian healthcare outcomes, particularly for organ support in critically injured warfighters, drives the research of David Burmeister, Ph.D., associate professor of Medicine and Surgery at the Uniformed Services University (USU), principal investigator at the Armed Forces Radiobiology Research Institute (AFRRI), and scientific director of the Battlefield Shock and Organ Support Program in USU’s Department of Surgery. His work on preclinical and translational trauma models focuses on systemic responses to various types of trauma, including thermal burns, radiation exposure, and hemorrhagic shock. These models replicate real-world scenarios to investigate potential therapeutic interventions.  

Dr. David Burmeister (Courtesy photo)

Multiorgan dysfunction is a major cause of morbidity and mortality following traumatic injury, necessitating early identification and aggressive management. One of the most common occurrences in multiorgan dysfunction is acute kidney injury, which occurs in nearly a third of combat casualties. In healthy individuals, the kidneys’ filtering function is very metabolically demanding, and therefore requires a lot of blood, particularly for filtering purposes. Because of that, they are one of the first organs to be affected by low blood flow and are susceptible to hemorrhage.  

Burmeister’s current research investigates the use of canagliflozin, an FDA-approved SGLT2 inhibitor prescribed for diabetes that has been shown to reduce chronic kidney disease in those patients. Given the effects on chronic kidney function, his team is examining its potential efficacy in preventing acute kidney injury. This additional benefit was discovered by using a novel noninvasive ischemia reperfusion model.  

Burmeister’s lab uses a model that involves inserting a balloon catheter to induce and release renal artery occlusion. The balloon catheter is inflated on top of the renal arteries for 90 minutes to restrict blood flow. In some experiments, canagliflozin is administered before the balloon catheter is released, reintroducing the drug to the kidneys. The researchers demonstrate reduced kidney structural damage and improved kidney function with canagliflozin.  

The implications are vast because canagliflozin has emerged as a potential therapeutic agent for acute kidney injury, including in renal transplantation, cardiopulmonary bypass, and aortic repair. This is in addition to prospective applications in trauma settings where acute kidney injury is a common complication. Beyond its role in diabetes, canagliflozin has demonstrated efficacy in lowering the risk of end-stage kidney disease, preventing the exacerbation of kidney function, and reducing the risk of heart attack, stroke, and blood vessel disease. These findings suggest that canagliflozin could be repurposed for a wider range of clinical applications, particularly in trauma and kidney injury.  

Severe renal ischemia reperfusion injury – when blood flow to the kidneys is temporarily blocked (ischemia) and then restored (reperfusion).– often complicates many high-risk surgical procedures, including renal transplant surgery, cardiopulmonary bypass, and aortic aneurysm repair. The resulting acute kidney injury seems to be an ongoing surgical challenge for those requiring renal replacement therapy. In trauma, severe ischemia reperfusion injury has affected treatments that have resulted in acute kidney injury in many cases. An accepted treatment for severe ischemia reperfusion injury does not currently exist, and new approaches are urgently needed.  

Burmeister says, “This research is significant because of its potential to improve kidney perfusion and transplantation outcomes, benefiting both the military and civilian sectors.”  

“Hopefully, this research can save, extend, or improve lives, particularly for active duty individuals,” Burmeister adds.  

His lab also investigates controlled and uncontrolled hemorrhagic shock models, examining uncontrolled junctional hemorrhage and abdominal hemorrhage. These types of hemorrhage are not treatable with tourniquets, thus endovascular strategies like resuscitative endovascular balloon occlusion of the aorta (REBOA) can be very valuable. In both the military and civilian worlds, when patients experience a temporary loss of blood flow (e.g., during a cardiopulmonary bypass, or being on the heart‒lung machine, or having a kidney transplant, etc.), having strategies to improve perfusion and transplantation could reduce organ damage.  

“More than 100,000 patients are on the waitlist for a kidney transplant, so you can see how important this is,” Burmeister notes.  

Canagliflozin also significantly reduces structural and functional damage in the kidneys. This suggests intrinsic renoprotective properties and improved acute kidney injury outcomes. The researchers observe increased creatinine clearance and decreased kidney biomarker damage in the urine.  

Burmeister’s lab is exploring other drugs in the same medication class to see what else could be of therapeutic use. 

Burmeister says that research can be difficult due to numerous intangibles. As a scientist, he attempts to try and control as many variables as he can.  

Safety first as staff dons lead aprons for fluoroscopy. (l to r) John Mares, Alec Kersey,

Justin Hutzler, Alexis Lauria, and David Burmeister. (Courtesy photo)

Further research is needed to fully elucidate the mechanisms by which canagliflozin protects against acute kidney injury and other kidney complications. Initial data from this study has shown that the mechanism of action involves the mitochondria and ensuing effects on cell death (i.e., apoptosis and mitophagy). More research figuring out the mechanism is necessary to evaluate the safety and efficacy of canagliflozin, as well as to identify new therapeutic targets in kidney injury.  

“When I did postdoctoral work at the U.S. Army Institute of Surgical Research, it was the first time I’d ever come face to face with combat casualties,” Burmeister recalls. “I saw the soldiers arriving with extreme injuries. I realize how profound some of these overall body responses to trauma are and how they could affect different organ systems,” Burmeister says. “Then, I begin to think physiologically about that and about what things we can do for it.”  

Burmeister maintains, “I hope that something we uncover in our research saves others.”  

“I think the potential for making a difference is what keeps me going in my research, as well as the potential to touch lives directly from a trauma standpoint, but also indirectly by looking at the training and education of our next generation of researchers,” Burmeister adds. “And, as a researcher, you never stop learning.”