A team from the University of Edinburgh found that patients with AKI had increased blood levels of endothelin – a protein that activates inflammation and causes blood vessels to constrict. Endothelin levels remained high long after kidney function had recovered.
After finding the same increase in endothelin in mice with AKI, experts treated the animals with medicines that block the endothelin system. The medicines – normally used to treat angina and high blood pressure – work by stopping the production of endothelin or by shutting off endothelin receptors in cells.
The mice were monitored over a four-week period after AKI. Those that were treated with the endothelin-blocking medicines had lower blood pressure, less inflammation and reduced scarring in the kidney.
Pharmacologic Treatment of Acute Kidney Injury
Their blood vessels were more relaxed and kidney function was also improved, compared with untreated mice.
The study is published in Science Translational Medicine. It was funded by the Medical Research Council and the British Heart Foundation.
Dr Bean Dhaun, Senior Clinical Lecturer and Honorary Consultant Nephrologist at the University of Edinburgh’s Centre for Cardiovascular Science, said: “AKI is a harmful condition, particularly in older people and even with recovery it can have a long-term impact on a person’s health. Our study shows that blocking the endothelin system prevents the long-term damage of AKI in mice. As these medicines are already available for use in humans, I hope that we can move quickly to seeing if the same beneficial effects are seen in our patients.”
Professor James Leiper, Associate Medical Director at the British Heart Foundation, said: “Impaired kidney function that results from acute kidney injury can also increase a person’s chance of developing and dying from heart and circulatory diseases, so it’s vital we find ways to reduce this risk.
“While further studies will be needed to demonstrate whether this treatment is safe and effective for patients, this early research is an encouraging first step.”
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