Scientists from the University of Virginia Health System and Mount Sinai have uncovered why those with chronic kidney disease so often die from heart problems. Their work, published in Circulation, describes how damaged kidneys release tiny particles into the bloodstream that are actively poisoning the heart. These tiny particles are only produced by diseased kidneys, and they carry genetic materials that disrupt heart function and can lead to heart failure.
“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.”
Chronic Kidney Disease and Heart Failure
Recent statistics estimate that chronic kidney disease affects around 1 in 7 people in the U.S., which translates to roughly 35.5 million Americans, according to the National Institutes of Health, with up to 90% of those with chronic kidney disease being unaware that they even have it. Chronic kidney disease is especially common among those with other health issues. For example, around 1 in 3 people with diabetes and about 1 in 5 people with high blood pressure (hypertension) also have kidney disease.
It has been established that chronic kidney disease and cardiovascular disease are closely connected, with more severe kidney damage being linked to worse heart outcomes. But understanding exactly why this happens has been unclear. Overlapping risk factors such as obesity and high blood pressure can make it hard to determine whether or not the kidneys themselves play a direct role in harming the heart.
Specific Kidney Cause Identified
This paper describes identifying a kidney-specific factor that directly damages the heart, pointing to a clear culprit: diseased kidneys release tiny particles that are known as circulating extracellular vesicles into the bloodstream, which are poisoning the heart.
Extracellular vesicles are produced by almost all cells, and they would typically act as messengers, transporting proteins and materials between cells. However, in those with chronic kidney disease, they carry small non-coding RNA known as miRNA that have now been found to be toxic to heart tissue, according to Erdbrügger and her colleagues.
Collecting Evidence
Experiments with mice showed that preventing these extracellular vesicles from circulating in the bloodstream led to noticeable improvements in heart function and reduced signs of heart failure.
Blood plasma sample analysis from those with and without chronic kidney disease revealed that the harmful extracellular vesicles can be found in those with kidney disease but not in healthy individuals.
“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.”
Early Detection and Treatments
Based on the findings, the researchers suggest that a blood test could be developed to identify those with chronic kidney disease who are at the highest risk of heart problems. Therapies could also be developed to block or neutralize the harmful circulating extracellular vesicles to reduce their damaging effects on the heart. Moving forward, Erdbrügger is developing a hands-on workshop that is focused specifically on this extracellular vesicle research.
“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.”
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