Acute kidney injury, or AKI, is a dangerous condition that affects many people in hospitals, especially those in intensive care or recovering from serious medical events like heart surgery or infections.
AKI can lead to long-term kidney damage and increase the risk of chronic kidney disease. Right now, there are no approved drugs to treat it.
Researchers at University of Utah Health have found a promising way to prevent AKI using a compound that targets a group of fatty molecules known as ceramides. These molecules were shown to harm the kidney’s energy-producing structures, the mitochondria. When the researchers blocked ceramides, they completely prevented kidney injury in mice.
Dr. Scott Summers, senior author of the study and Chair of the Department of Nutrition and Integrative Physiology at the University of Utah, was surprised by the results. “We completely reversed the pathology of acute kidney injury by inactivating ceramides,” he said. “Not only did kidney function stay normal, but the mitochondria were unscathed.”
The research was published in the journal Cell Metabolism.
The study builds on earlier work from Dr. Summers’ lab, which showed that ceramides can damage other organs like the heart and liver. When the team examined ceramide levels after kidney injury, they found that the levels shot up quickly in both mice and human urine samples.
The more severe the injury, the higher the ceramide levels. This means ceramides could also serve as an early warning sign or biomarker for AKI, helping doctors identify at-risk patients before symptoms appear.
To test their theory, the researchers first altered the genes in mice to reduce ceramide production. These “super mice” were resistant to kidney damage, even under extreme stress.
Then, the team gave normal mice a drug candidate developed by Centaurus Therapeutics—a company co-founded by Summers—that lowers ceramide levels. The drug protected the kidneys, kept function normal, and prevented damage to the mitochondria.
“The mice looked incredible,” Summers said. They remained active and showed almost no signs of injury, even under intense conditions that would normally cause serious damage.
The key discovery was that ceramides disrupt mitochondria in kidney cells. Mitochondria are vital for supplying energy, and when damaged, the cells can’t function properly. The drug helped preserve these structures and keep the cells working, even during high stress.
Although the compound used in the study is not the exact one currently being tested in human trials, it’s closely related. Summers emphasized that more research is needed to make sure it’s safe for people. “We’re thrilled by how protective this compound was, but it’s still preclinical,” he cautioned.
Still, the potential impact is big. If this approach works in humans, it could be used to protect people at high risk of AKI, like those having heart surgery. Since the treatment helps keep mitochondria healthy, it might also be useful in other conditions tied to mitochondrial problems—such as heart failure, diabetes, and fatty liver disease.
“Mitochondrial issues are common in many illnesses,” Summers said. “If we can restore mitochondrial health, it could lead to new treatments for many serious conditions.”
If you care about kidney health, please read studies about drug that prevents kidney failure in diabetes, and drinking coffee could help reduce risk of kidney injury.
For more information about kidney health, please see recent studies about foods that may prevent recurrence of kidney stones, and common painkillers may harm heart, kidneys and more.
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