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

A complex and often deadly condition, AKI typically occurs as a secondary effect of another major health issue, such as when an patient undergoes a major surgery, suffers a traumatic accident or contracts sepsis.

AKI 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.

This could hopefully change in the near future thanks to some unexpected research findings from Sylvie Breton, PhD, who may have found a way to track the silent killer through her research into cell sensing and pH balance in the kidneys.

Breton, an Investigator at the Center for Systems Biology at Massachusetts General Hospital and 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 the cells’ ability to detect changes in pH levels.

During their study, they found that these cells expressed high levels of a receptor that senses a “danger signal” molecule the body releases when it is under stress.

This danger molecule circulates throughout the body and accumulates in the kidneys, where it is condensed and amplified as pre-urine is being formed.

The molecule binds to the highly active receptors in these cells, which starts an inflammatory response that leads to kidney damage and AKI.

While Breton and her team weren’t targeting AKI in their study, they knew they had to pursue their finding.

“In science, 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 the buildup of this danger molecule in the urine of patients a day or two before they develop AKI. Early detection could give doctors a window to halt the process before it causes damage to the kidneys.

Breton has since co-founded a startup company that is working to translate these insights into new diagnostic tools and treatments for patients.

They are developing a molecule that could block the receptor in kidney cells that binds to the danger molecule, which could reduce the inflammatory process that leads to kidney damage.

“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

Endowed Chair Provides Crucial Support

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 that may be too early or premature for traditional forms of research funding through the National Institute of Health.

“IIf I have an idea, I don’t have to necessarily have 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.”

About the Mass General Research Institute
Research at Massachusetts General Hospital is interwoven through more than 30 different departments, centers and institutes. Our research includes fundamental, lab-based science; clinical trials to test new drugs, devices and diagnostic tools; and community and population-based research to improve health outcomes across populations and eliminate disparities in care.
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