Doctors have long known that chronic kidney disease can sharply increase a patient’s risk of heart failure. More than half of people with advanced kidney disease ultimately die from cardiovascular complications, even when obesity, hypertension and diabetes do not fully explain the connection.
Researchers at the University of Virginia and Icahn School of Medicine at Mount Sinai in New York now say they have identified a kidney-specific mechanism that may help solve the puzzle.
The team found that diseased kidneys release large numbers of circulating extracellular vesicles, or microscopic particles that act as messengers between organs.
Nearly all cells in the body shed these vesicles, which carry biological “cargo” such as proteins and genetic material.
In healthy people, those signals may help maintain normal communication. But in people with chronic kidney disease, the vesicles appear to carry toxic microRNA, small molecules that regulate gene activity and protein production.
When those vesicles reach the heart, they can disrupt normal function and contribute to the development of heart failure.
Uta Erdbrügger, the study researcher and a UVA physician-scientist, said the discovery could help doctors detect cardiovascular risk earlier, even before patients develop symptoms.
“So if we identify patients who don't have any symptoms that they're at risk for heart disease, we can intervene sooner,” she said.
She said the discovery offers the first direct evidence that the kidney can actively influence heart damage through long-distance organ-to-organ signaling.
“Normally, each cell communicates with the neighboring cells, but this is much further away,” Erdbrügger said. “I find it very fascinating taking care of these patients, and it will help with precision medicine.”
In experiments on mice, scientists reduced the amount of these vesicles circulating in the blood and saw heart function improve. The team also confirmed the presence of harmful vesicles in blood samples from patients with chronic kidney disease.
The team reduced the vesicles circulating in the mice’s blood using a broad drug intervention that was not designed to target one specific pathway.
“So this was not a very targeted, specific treatment,” Erdbrügger said. “It was in general, for all vesicles, so we had less vesicles, but we could show that the heart failure didn't appear as strongly in those mice.”
Erdbrügger said one of the most urgent goals is developing earlier tools to identify patients at risk. Kidney disease and heart failure often progress silently, and current clinical markers tend to rise only after significant damage has already occurred.
She said the findings could eventually lead to a blood test that detects hidden heart failure risk in kidney patients, so clinicians can start treatment sooner.
Before that can happen, Erdbrügger said researchers must validate the marker in much larger studies. Her team is now planning “deep phenotyping,” using imaging and detailed evaluations to track heart disease in kidney patients and test the vesicles in cohorts of thousands.
She estimated it could take five to 10 years of additional research before the discovery reaches routine clinical care.
The biggest obstacle, she said, is funding: Large multi-site studies can cost millions of dollars and often require support from both the National Institutes of Health and private foundations.
The research was published in the journal Circulation.
