Chronic Kidney Disease Poisons Hearts: Scientists Uncover the Cause

Scientists have discovered an answer to the longstanding mystery of why more than half of patients with chronic kidney disease ultimately die of cardiovascular problems: Their kidneys produce a substance that poisons the heart. The researchers, at UVA Health and Mount Sinai, say the discovery could let doctors identify people at risk and develop new treatments to help prevent and treat heart failure for these patients. The work is published in the journal Circulation. "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 in chronic kidney disease Chronic kidney disease affects more than 1 in 7 Americans – approximately 35 million people in the United States, according to the National Institutes of Health. About 1 in 3 patients with diabetes and about 1 in 5 people with hypertension (high blood pressure) have kidney disease, the agency reports. The link between chronic kidney disease (CKD) and cardiovascular problems has been well documented, with the severity of cardiovascular disease correlating directly with CKD. But scientists have struggled to understand why, partly because shared risk factors such as obesity and hypertension muddy the waters when it comes to determining cause and effect. Scientists had, until now, been unable to pinpoint any kidney-specific risk factor that could be causing toxicity in the heart. But the new research from Erdbrügger and colleagues identifies a culprit: particles called "circulating extracellular vesicles" produced in diseased kidneys. Extracellular vesicles are produced by almost all cells and serve as important messengers by carrying proteins and other materials to other cells. But the extracellular vesicles produced in kidneys with CKD carry small, non-coding RNA called miRNA that are toxic to the heart, the researchers determined. In lab mice, blocking the extracellular vesicles from circulating significantly improved heart function and alleviated heart failure. The scientists also looked at blood plasma samples donated by patients with CKD and by healthy patients and confirmed the presence of harmful extracellular vesicles in the CKD patients. "Doctors have 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 of understanding this communication." The results, she said, suggest that scientists may be able to develop a blood test to identify CKD patients at high risk for serious heart problems. They also may be able to target the circulating extracellular vesicles to treat or prevent the poisonous effects on the heart. "Our hope is to develop novel biomarkers and treatment options for our kidney patients at risk for heart disease," she said. "Potentially our work will improve precision medicine for CKD and Heart failure patients, so that each patient gets the exact treatment they need."