Existing Drugs Show Promise for Treating Acute Kidney Injury

Researchers in Scotland report that acute kidney injury (AKI)—a common illness that can cause the kidneys to stop working—can be treated with already approved medicines for angina and high blood pressure. The findings are a breakthrough for treating AKI—which occurs in 20% of the United Kingdom’s emergency hospital admissions—and preventing the long-term damage to the kidney and cardiovascular system associated with the disease.

AKI develops when other illnesses reduce blood flow to the kidney, and it can also arise due to toxicity from some medications. It must be treated quickly to prevent death. Of those who survive an episode of AKI, 30% are left with chronic kidney disease (CKD). The remaining 70% that recover full kidney function are at an almost 30-fold increased risk of developing CKD.

The University of Edinburgh team 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, they treated the animals with medicines that block the endothelin system. The drugs, which are 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. Their blood vessels were more relaxed and kidney function was also improved, compared with untreated mice.

“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,” says Dr. Bean Dhaun, Senior Clinical Lecturer and Honorary Consultant Nephrologist at the University of Edinburgh’s Centre for Cardiovascular Science. “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.”

The study was published recently in Science Translational Medicine.