Scientists have uncovered a key reason why more than half of people with chronic kidney disease eventually die from heart-related complications. According to new research, damaged kidneys release a substance into the bloodstream that directly harms the heart.
The discovery, made by researchers at UVA Health and Mount Sinai, could help doctors spot high-risk patients earlier and open the door to new treatments aimed at preventing or slowing heart failure in people with kidney disease.
“Kidney and heart disease can develop silently, so they are often discovered only after damage has already been done,” said researcher Uta Erdbrügger, MD, an internal medicine physician-scientist with the University of Virginia School of Medicine’s Division of Nephrology. “Our findings can help to identify patients at risk for heart failure earlier, enabling earlier treatment and improved outcomes.”
Heart Failure Risk in Chronic Kidney Disease
Chronic kidney disease affects more than 1 in 7 Americans, or roughly 35 million people in the United States, according to the National Institutes of Health. The condition is especially common among people with other health issues. About 1 in 3 patients with diabetes and around 1 in 5 people with hypertension (high blood pressure) also have kidney disease.
Doctors have long known that chronic kidney disease and cardiovascular disease are closely connected, with more severe kidney damage linked to worse heart outcomes. However, understanding exactly why this happens has been difficult. Many patients share overlapping risk factors such as obesity and high blood pressure, making it hard to determine whether the kidneys themselves play a direct role in harming the heart.
A Kidney-Specific Cause Identified
Until now, researchers had not been able to identify a kidney-specific factor that directly damages the heart. The new study led by Erdbrügger and her colleagues points to a clear culprit. Diseased kidneys release tiny particles known as “circulating extracellular vesicles” into the bloodstream.
Extracellular vesicles are produced by nearly all cells and normally act as messengers, transporting proteins and other materials between cells. In people with chronic kidney disease, however, these vesicles carry small, non-coding RNA called miRNA that the researchers found to be toxic to heart tissue.
Lab and Patient Evidence
In laboratory mice, preventing these extracellular vesicles from circulating led to noticeable improvements in heart function and reduced signs of heart failure. The research team also analyzed blood plasma samples from people with chronic kidney disease and from healthy individuals. Harmful extracellular vesicles were found in patients with kidney disease but not in healthy volunteers.
“Doctors always wondered how organs such as the kidney and heart communicate with each other. We show that EVs from the kidney can travel to the heart and be toxic,” Erdbrügger said. “We are just at the beginning to understand this communication.”
Toward Earlier Detection and New Treatments
The findings suggest that a blood test could one day be developed to identify people with chronic kidney disease who face the highest risk of serious heart problems. Researchers may also be able to design therapies that block or neutralize these circulating extracellular vesicles, reducing their damaging effects on the heart.
“Our hope is to develop novel biomarkers and treatment options for our kidney patients at risk for heart disease,” Erdbrügger said. “Potentially our work will improve precision medicine for CKD and Heart failure patients, so that each patient gets the exact treatment they need.”
Advancing Extracellular Vesicle Research
To help move this field forward, Erdbrügger is organizing a hands-on workshop for UVA scientists focused specifically on extracellular vesicle research. The five-day workshop begins Feb. 7.
Finding answers to the most pressing medical mysteries and developing new treatments for complex diseases are key goals of UVA’s new Paul and Diane Manning Institute of Biotechnology. The institute is designed to speed the transition from laboratory discoveries to real-world therapies that can save lives.
Findings Published
The research findings were published in the scientific journal Circulation. The article is open access, meaning it is available to read for free.
The research team included Xisheng Li Nikhil Raisinghani, Alex Gallinat, Carlos G. Santos-Gallego, Shihong Zhang, Sabrina La Salvia, Seonghun Yoon, Hayrettin Yavuz, Anh Phan, Alan Shao, Michael Harding, David Sachs, Carol Levy, Navneet Dogra, Rupangi Vasavada, Nicole Dubois, Erdbrügger and Susmita Sahoo. The scientists reported no financial conflicts of interest.
The study was funded by the National Institute of Health through grants HL140469, HL124187, HL148786, R01DK125856, 1-INO-2025-1704-A-N, R21AG07848, and R01DK133598.
