A serious condition that causes the kidneys to stop working suddenly can be treated with existing drugs, new research suggests.

In a study of mice, scientists found that drugs commonly used to treat angina and high blood pressure prevented long-term damage to the kidneys and cardiovascular system in acute kidney injury (AKI).

Experts hope the discovery will pave the way for improved treatment of AKI – a common condition that accounts for approximately 20 per cent of emergency hospital admissions in the UK.

The disease is usually caused by other diseases that reduce blood flow to the kidneys or by toxins produced by certain drugs.

AKI must be treated quickly to prevent death. Even if the kidneys recover, AKI can cause long-term damage to the kidneys and cardiovascular system.

Among survivors of an AKI episode, 30 percent develop chronic kidney disease (CKD). The remaining 70 percent have full recovery of kidney function and are 30 times more likely to develop CKD.

A team from the University of Edinburgh found that AKI patients had increased levels of endothelin – a protein that activates inflammation and causes blood vessels to dilate. Endothelin levels remained high after recovery of renal function.

After finding a similar increase in endothelin in mice with AKI, experts treated the animals with drugs that block the endothelin system. The drugs – commonly used to treat angina and high blood pressure – work by stopping the production of endothelin or by blocking endothelial receptors in the cells.

The mice were monitored for four weeks after AKI. Those treated with endothelin-blocking drugs had reduced blood pressure, inflammation, and kidney scarring.

Compared to untreated mice, their blood vessels relaxed more and their kidney function improved.

The study was published in Science Translational Medicine. Funded by the Medical Research Council and the British Heart Foundation.

AKI is a harmful condition, especially in older people, and even with recovery, it can have long-term effects on a person’s health. Our study shows that inhibition of the endothelin system prevents the long-term damage of AKI in rats. I hope we can move quickly to see the same beneficial effects in our patients as these drugs are used in humans.”


Dr Bin Down, Senior Clinical Lecturer and Honorary Consultant Nephrologist, University of Edinburgh Center for Cardiovascular Sciences

Professor James Leiper, associate medical director at the British Heart Foundation, said: “The deterioration of kidney function caused by kidney disease increases a person’s risk of cardiovascular disease and death, so it is very important to find ways to reduce this risk.

“This promising study suggests that widely available medications can help prevent the effects of acute kidney injury before it causes further complications. Further studies are needed to ensure that this treatment is safe and effective for patients, and this early study is an encouraging first step.”

Source:

Journal Reference:

Zopec, A., inter alia. (2022) Endothelin blockade prevents long-term cardiovascular and renal consequences of acute kidney injury in rats. Science Translational Medicine. doi.org/10.1126/scitranslmed.abf5074.

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