For years, scientists have been working to unravel the mystery of patients with failing kidneys dying from heart-related complications.
Researchers now say they’ve uncovered a clue that explains why people with chronic kidney disease have such a high risk of heart failure — and it could have major implications for the diagnosis and treatment of the two common health conditions.
A new study found that diseased kidneys released tiny particles that were toxic to the heart, according to findings published recently in the peer-reviewed journal Circulation.
“We went on a mission to understand this interorgan communication between the kidney and the heart,” said Uta Erdbrügger, an associate professor of medicine at the University of Virginia School of Medicine who co-authored the study. “We found that there are molecules communicating between the kidney and the heart.”
That molecular discovery is helping to shed light on one way the kidney and heart are linked — and, in this case, to dangerous effect, said Susmita Sahoo, the study’s senior author and an associate professor of medicine at the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai.
“No one has shown this causal relationship before,” Sahoo said.
The kidney-heart connection
The relationship between chronic kidney disease and heart conditions is well documented. Studies showthat the severity of cardiovascular complications is correlated with the stage of kidney failure. Some estimates suggestthat more than half of people with advanced kidney disease develop cardiovascular problems.
“Heart failure and kidney disease are very, very closely intertwined conditions,” said Janani Rangaswami, a nephrologist and professor of medicine at the George Washington University School of Medicine who was not involved in the study. “Almost 1 in 2 individuals with heart failure will have some degree of kidney dysfunction, and kidney disease is a very powerful risk enhancer for the development of heart failure.”
Kidney failure causes bodies to retain fluid, which can put more strain on the heart muscle, said Samir Parikh, president of the American Society of Nephrology. Kidney disease can also cause electrolyte imbalances, which can lead to dangerous heart rhythms, he said. The condition is also associated with accelerated hardening of arteries that can result in heart attacks.
“Each step that you lose kidney function is just a greater and greater stress on the heart,” Parikh said. “The kidney really has this profound influence on the health of the heart in all of its dimensions.”
The correlation between kidney and heart problems can also trace to shared risk factors, such as hypertension, smoking and diabetes. But the study’s author said that hypothesis can’t fully explain why kidney patients are more likely to also have heart failure.
Studying the link
In search of answers, the researchers homed in on microscopic liquid-filled sacs that are produced by almost all cells and serve as messengers in the body. Known as extracellular vesicles, the particles shuttle proteins and other materials between cells and organs.
The scientists collected blood samples from about 50 people, including those with varying degrees of kidney disease as well as healthy subjects. They observed that the blood from sick people contained vesicles carrying a type of noncoding RNA, the genetic material that orchestrates basic life activities, that had a toxic effect on heart tissue. They noted these harmful vesicles were being produced by the damaged kidneys and were not found in blood samples from healthy patients.
In early lab tests using mice, the researchers discovered that reducing extracellular vesicles in the blood using a drug led to improved heart function and fewer signs of heart failure even in mice with diseased kidneys.
Changing care
Rangaswami said the study was “very scientifically rigorous” and addressed a scientific gap in understanding kidney-specific factors harming the heart.
“That’s a very poorly understood area in this whole nexus of heart-kidney disease,” she said.
Sahoo said her team’s findings could help identify heart disease in kidney patients earlier, before they show symptoms.
“By measuring these cardiotoxic microRNAs, you can actually predict or identify or diagnose the patient who are on the way to developing a failing heart,” she said.
The research can also influence treatment recommendations, said Erdbrügger, the study co-author who is also a practicing kidney doctor. For instance, Erdbrügger said if she knew one of her kidney patients had a higher risk of heart disease, she would consider treating more aggressively by increasing drug dosages or using more combinations of medications.
“We are really going towards precision medicine,” she said. “The better we understand the pathophysiology or the mechanisms, the better we can intervene and develop a new drug.”
But she and other experts cautioned that more research is needed.
“These are potential biomarkers and potential therapeutic targets,” said Joseph Vassalotti, chief medical officer of the National Kidney Foundation, who was not involved in the study. “This is all preliminary, and there’s a lot of additional work that would need to be done to validate these findings, and to see if they apply diagnostically and therapeutically.”
Erdbrügger said scientists are working on a much larger, longer-term study to track whether people with chronic kidney disease develop heart conditions.
Know your risk
In the meantime, experts urge people to stay on top of monitoring their kidney health.
It’s critical to know your chances of developing kidney disease, Parikh said. He added that simple blood and urine tests can diagnose the condition.
Some risk factors include:
- Diabetes
- High blood pressure
- A family history of kidney disease or failure
- For women, adverse pregnancy conditions such as gestational diabetes and preeclampsia
If you have any of those risk factors, Rangaswami recommended talking to a clinician about monitoring your kidney health.
“When we think about kidney health, we have to understand that preserving kidney health is so important to preserving heart health,” Rangaswami said. “We have so many amazing therapies that can really stabilize kidney function.”
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