Scientists Reverse Kidney Damage in Mice, Paving Way for Human Trials

Researchers at the University of Utah Health have made a significant breakthrough in reversing acute kidney injury, or AKI, in mice. According to a study published in Cell Metabolism, AKI can be a life-threatening condition that often leads to chronic kidney disease, yet no approved medications currently exist to treat it.

The study identifies fatty molecules known as ceramides as key contributors to AKI, as they damage the mitochondria, which are essential for energy production in kidney cells. The research team, led by Dr.

Scott Summers, discovered that by altering the processing of ceramides using a drug candidate, they could protect mitochondrial integrity and prevent kidney injury in mouse models. In their experiments, they found that not only did the mice maintain normal kidney function, but their mitochondria were also unaffected by the injury.

Dr. Summers expressed his astonishment, stating, 'We completely reversed the pathology of acute kidney injury by inactivating ceramides.' The study also noted that ceramide levels in urine could serve as an early biomarker for AKI, allowing healthcare providers to identify at-risk patients before symptoms arise.

For instance, patients undergoing high-risk procedures like heart surgery could be monitored for elevated ceramide levels, enabling preemptive measures. In a further exploration of their findings, the researchers created genetically modified mice that were resistant to AKI, showcasing remarkable resilience even under conditions known to induce severe kidney damage.

They also tested a ceramide-lowering drug candidate from Centaurus Therapeutics, co-founded by Dr. Summers, which showed promising results in preventing kidney injury. Mice treated with this drug maintained normal kidney function and exhibited healthy kidney structures.

Dr. Summers highlighted the potential for this approach to extend beyond kidney health, suggesting it might also benefit other diseases associated with mitochondrial dysfunction, such as heart failure and diabetes.

While the results are promising, the researchers caution that further preclinical studies are required to ensure safety before advancing to human trials, emphasizing the importance of due diligence in testing.

The research was supported by several grants from the National Institutes of Health and various foundations, with Dr. Summers and his colleagues noting that their findings could pave the way for future therapies targeting mitochondrial health.

This breakthrough could be transformative for patients at high risk for AKI, potentially changing the landscape of treatment options in a field that currently lacks effective therapies.