Researchers have unearthed the explanation for why over half of individuals suffering from chronic kidney disease (CKD) ultimately succumb to cardiovascular issues: their kidneys generate a substance that poisons the heart.
Investigators from UVA Health and Mount Sinai assert that this breakthrough will equip clinicians to pinpoint at-risk individuals and devise novel therapeutic strategies to avert and address heart failure in these patients. The findings have been published in the journal Circulation.
“Kidney and heart ailments can progress silently, meaning they are often only discovered after damage has already occurred,” notes study co-author Uta Erdbruegger from the University of Virginia School of Medicine. “Our results hold the potential to identify patients susceptible to heart failure at earlier stages, enabling prompt treatment initiation and improved outcomes.”
According to the National Institutes of Health, chronic kidney disease impacts more than one in seven Americans—approximately 35 million people in the United States. Roughly one in three individuals with diabetes and about one in five persons with hypertension (high blood pressure) are diagnosed with kidney disease, the agency reports.
The link between chronic kidney disease (CKD) and cardiovascular disease is well-established, showing a direct correlation between the severity of heart conditions and the level of CKD. However, scientists have consistently struggled to comprehend the underlying reasons, partly because shared risk factors like obesity and elevated blood pressure obscure the establishment of direct causation.
Until now, researchers had failed to isolate any kidney-specific risk factor that could precipitate toxic effects on the heart. But the new study led by Erdbruegger and her colleagues has identified the culprit: particles termed “circulating extracellular vesicles” that originate from the compromised kidneys.
Extracellular vesicles are produced by almost all cells and serve as crucial messengers, ferrying proteins and other materials to distant cells. Nevertheless, the research team discovered that the extracellular vesicles generated by kidneys afflicted with CKD carry small non-coding RNAs, known as microRNAs, which are cardiotoxic.
In experiments conducted on laboratory mice, inhibiting the circulation of these extracellular vesicles led to substantial improvements in heart function and alleviated heart failure symptoms. The scientists also analyzed plasma samples provided by both CKD patients and healthy controls, confirming the presence of these detrimental extracellular vesicles in those with CKD.
“Clinicians have long puzzled over the communication pathways between organs like the kidneys and the heart. We have demonstrated that extracellular vesicles originating from the kidneys can travel to the heart and exert a toxic effect,” states Erdbruegger. “We are only at the beginning of understanding this interplay.”
These findings suggest the possibility of developing a blood test to screen CKD patients who face elevated risks of severe cardiac complications. Furthermore, it may become feasible to target these circulating extracellular vesicles to treat or prevent their toxic impact on the heart.
“Our hope is to develop new biomarkers and therapeutic avenues for our patients with kidney disease who are vulnerable to cardiovascular issues,” Erdbruegger concludes. “Potentially, our work will advance personalized medicine for individuals managing chronic kidney disease and heart failure, ensuring each patient receives precisely the intervention they require.”
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