Protecting Kidneys Before Damage: A New Approach to Acute Kidney Injury
researchers have identified a key molecule, ceramide, as a critical player in the advancement of acute kidney injury (AKI), and have demonstrated a promising preventative strategy in preclinical studies. The findings, published in Cell Metabolism, suggest a future where at-risk patients coudl receive treatment before procedures known to strain the kidneys, significantly reducing their chances of developing this potentially serious complication.
AKI, a sudden decline in kidney function, often occurs following major surgery, particularly heart procedures, affecting up to a quarter of patients. Currently, diagnosis often happens after symptoms appear, limiting treatment options. However, this new research focuses on prediction and prevention. By identifying individuals at high risk – those undergoing procedures known to stress the kidneys – researchers hope to proactively intervene.
The team, led by researchers at the University of utah, discovered that manipulating ceramide production can dramatically protect kidney function. In a mouse model, genetically modifying the process of ceramide creation resulted in “super mice” wholly resistant to AKI, even under conditions that typically cause severe kidney damage. Further testing with a ceramide-lowering drug candidate from Centaurus Therapeutics yielded similarly impressive results. Mice treated with the drug prior to kidney stress maintained normal function, remained active, and showed minimal kidney damage under microscopic examination.
The protective effect appears to stem from ceramide’s impact on mitochondria, the powerhouses of cells. The research revealed that ceramides disrupt mitochondrial function in kidney cells, leading to distortion and reduced energy production. By lowering ceramide levels, either genetically or pharmacologically, the team was able to preserve mitochondrial integrity and function even under duress.
While the drug used in the study is related to a compound currently in human clinical trials,researchers emphasize the need for caution. ”Mouse results do not always predict human outcomes,” explains Scott Summers, co-founder of Centaurus Therapeutics, “and further research is needed to confirm safety.” Despite this, the team is optimistic. if prosperous in humans, this preventative approach could be a game-changer for patients facing high AKI risk.
Beyond AKI, the implications of this research could extend to a wider range of diseases. Mitochondrial dysfunction is implicated in conditions like heart failure, diabetes, and fatty liver disease. Restoring mitochondrial health, the researchers beleive, could offer a novel therapeutic avenue for these and other disorders.
Funding & Disclosures: This research was supported by numerous grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and several philanthropic organizations (detailed in the original article). Scott Summers,Jeremy Blitzer,and Liping Wang are co-founders and shareholders of Centaurus Therapeutics,and hold patents licensed to the company.
