How An Unexpected Finding Could Lead to New Ways to Predict and Prevent Acute Kidney Injury

There’s a good reason why acute kidney injury (AKI) is known as “the silent killer.”

A complex and often deadly condition, AKI usually occurs as a secondary effect of another major health issue, such as undergoing major surgery, getting injured in accidents or developing sepsis.

It kills more people than prostate cancer, breast cancer, heart failure and diabetes combined, and yet it often goes undetected until it’s too late because it has no symptoms.

Sylvie Breton, PhD, has found a way to track the silent killer through her research into cell sensing and pH balance in kidneys.

Breton, an Investigator in the Division of Nephrology at Massachusetts General Hospital and a Professor of Medicine at Harvard Medical School, recently shared the details of this discovery on Mass General’s Charged podcast, which profiles women who are driving change in healthcare.

An Unexpected Discovery

Breton and her research team were studying the genetic signatures of a subtype of kidney cells called intercalated cells with the goal of learning more about pH sensing. They found the cells expressed high levels of a receptor that senses a “danger signal” molecule the body creates when it is under stress.

This danger signal molecule circulates in the body and accumulates in the kidneys, where it gets amplified as pre-urine is being formed. The molecule binds to a highly active receptor in these cells, which starts an inflammatory response that leads to kidney damage.

Despite the unexpected nature of the finding, Breton and her team knew they had to pursue it.

“We need to listen to our results, explore what they’re telling us, and adjust our way of thinking accordingly,” she says. “I often think the breakthroughs in medicine or the major discoveries we make are the ones that we did not predict.”

Testing the Concept

In a small proof-of-concept study conducted with cardiac surgery patients at Mass General, Breton and colleagues found that it is possible to detect this danger molecule in the urine of patients a day or two before they develop AKI. Detecting this molecule soon enough could give doctors a window to stop the process before it becomes harmful to patients.

Breton co-founded a startup company that is working to turn these research insights into new diagnostic tools and treatments for patients. They are developing a molecule to block the receptor in the kidney cells that reacts to the danger molecule to prevent or reduce the inflammatory process that leads to AKI.

“In our labs we work in a bubble, so we now need to get this discovery out and developed, so it becomes a real medication and diagnostic for patients.”

Sylvie Breton, PhD

Researching the Causes of Male Infertility

While branching out into the drug development world is a new experience for Breton, she remains committed to her research work at Mass General, where she was recently named the inaugural Richard Moerschner Endowed MGH Research Institute Chair in Men’s Health.

In this role, she will continue to investigate the role of pH sensing in kidney cells as well as in the epididymis, a small tightly coiled organ that is responsible for the maturation and transportation of sperm from the testes to the vas deferens.

A better understanding of how the epididymis functions—and the relationship between pH balance and sperm maturation—could point to new treatments for male infertility.

The funding provided by the endowment will provide Breton with ongoing financial support she can use to pursue other unexpected findings in the lab that may be too early or premature for traditional forms of research funding.

“It’s a great honor first, and it’s humbling,” she says. “At the same time, you feel exhilarated, because it’s freeing up your brain.”

“If I have an idea, I don’t have to necessarily think about writing a proposal and convincing an expert to secure grant funding first. I have these funds that I can use to test these new ideas very quickly.”

Sylvie Breton, PhD

About the Mass General Research Institute
Massachusetts General Hospital is home to the largest hospital-based research program in the United States. Our researchers work side-by-side with physicians to develop innovative new ways to diagnose, treat and prevent disease.
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