Kidney Damage Reversed: Mice Study Offers Hope for Humans
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Ceramides Linked to Acute Kidney Injury – Potential for Early Detection and Treatment
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Serious injury to short-term kidney function, known as acute kidney injury (AKI), can be life-threatening and also raise the likelihood of developing permanent chronic kidney disease.AKI can occur after major stressors such as sepsis or heart surgery, and more than half of all intensive care patients experience it. No approved medications currently exist to treat this condition.
Researchers at University of Utah Health (U of U Health) have discovered that fatty molecules called ceramides initiate AKI by damaging the mitochondria that supply energy to kidney cells. by using a backup drug candidate designed to alter how ceramides are processed, the team protected mitochondrial structure and prevented kidney injury in mice.
“We wholly reversed the pathology of acute kidney injury by inactivating ceramides,” says Scott Summers,PhD,distinguished professor and Chair of the Department of Nutrition and Integrative Physiology in the University of utah Collage of Health and senior author on the study. ”We were stunned — not only did kidney function stay normal, but the mitochondria were unscathed,” Summers says. “It was truly remarkable.”
The results are published in Cell Metabolism.
Ceramide Spikes as an Early Warning Sign
Earlier studies from the Summers lab showed that ceramides can harm organs such as the heart and liver. When the researchers measured ceramides in AKI models, they found a strong connection: levels rose sharply after injury in both mice and in human urine samples.
“Ceramide levels are very elevated in kidney injury,” says Rebekah Nicholson, phd, first author on the work, who completed the research as a graduate student in nutrition and integrative physiology at U of U Health and is now a postdoctoral fellow at the Arc Institute.”They go up quickly after damage to the kidneys, and they go up in relation to the severity of the injury. The worse the kidney injury is, the higher the ceramide levels will be.”
These findings indicate that urinary ceramides could act as an early biomarker for AKI, giving clinicians a tool to identify vulnerable patients, including those preparing for heart surgery, before symptoms begin. “If patients are undergoing a procedure that we know puts them at high risk of AKI, then we can better predict whether or not they’re actually going to have one,” nicholson says.
Altering Ceramide Production Protects Kidney Function
The team nearly eliminated kidney injury