Circulating Extracellular Vesicles Contribute to Heart Failure Pathogenesis in CKD

Human and mouse models demonstrate that circulating chronic kidney disease (CKD) extracellular vesicles (EVs) carry small, noncoding miRNA that are toxic to the heart and contribute to the pathogenesis of heart failure (HF) in patients with CKD. When these miRNAs are blocked, heart function can be improved. The insights, garnered from data published by investigators in Circulation, provide a potential avenue for mediating the risk of cardiovascular disease in this patient population.^1,2

Why the Kidneys Can “Poison” the Heart of Patients With CKD

The investigators compared plasma EVs from patients with CKD with healthy controls, both in vitro and in vivo, to determine cardiotoxic function. To confirm the results and gain further insights, they utilized a mouse model and instigated HF with reduced cardiac function. A total of 35 patients with stable, moderate, or advanced CKD, plus 18 comparable controls, were included in the analysis.^1,2

Results demonstrated that circulating EVs from patients with CKD are cardiotoxic and can induce apoptosis, impair contractile function, and restrict calcium ions. The investigators characterized significant increases in human AC16 (hAC16)-cardiomyocyte (CM) death compared with healthy controls, which is an indicator of cardiotoxicity. They confirmed these results by treating adult rat primary CMs with CKD-EVs and, using the IonOptix Myocyte Calcium and Contractility System, determined that CKD-EVs can significantly impair the handling of calcium ions.¹

In mice, the investigators isolated plasma EVs from CKD mice and control mice at 8 weeks to determine whether circulating plasma in CKD mice is cardiotoxic. Mice with CKD-EVs had impaired cardiac function, and depleting circulating EVs in mice with CKD helped recover cardiac function and improve HF, even despite the presence of other CKD morbidities. Furthermore, they observed that CKD-EVs are enriched in cardiotoxic miRNAs that originate from kidney cells, suggesting both shared and distinct circulating miRNA cargo between mouse and human CKD-EVs.¹

Ultimately, the authors established that circulating CKD-EVs can play a causal role and significantly contribute to CKD-induced HF. The miRNAs produced in the kidney can significantly decrease the viability of hAC16-CM and carry CKD-EVs into the bloodstream and are clear and distinct from those of noncardiotoxic EVs. The investigators found that the expression of several CKD-miRNAs was meaningfully higher in EVs from both patients with CKD and HF and patients with CKD without HF, and that the expression of many CKD-EV-miRNAs correlated with markers of HF.^1,2

What Should Pharmacists Know About the Link Between HF and CKD?

The data provides health care professionals new methods to identify individuals with CKD at risk of HF pathogenesis while aiding in the development of new treatments to prevent and treat HF. The EV-containing miRNA produced by kidneys can “poison” the heart; early detection of patients at risk for HF is critical for earlier treatment and improved outcomes, according to Uta Erdbrügger, MD, an internal medicine physician-scientist with the University of Virginia School of Medicine’s Division of Nephrology.²

Erdbrügger highlighted the potential for earlier intervention in patients with CKD at risk of HF, which could mean improved outcomes.³

“We hope that we will develop biomarkers that tell us that a patient either is at risk or already has some underlying heart failure, which in some patients might be subclinical,” Erdbrügger explained. “If we have early markers of heart failure risk or even damage, we could then escalate drug treatment and intervene sooner—so early detection, early treatment—and therefore improve outcomes.”³

Pharmacists should know that patients with CKD are at a heightened risk of HF and utilize risk scores, along with nontraditional risk factors that are independent of kidney function, to identify more patients at earlier times. Erdbrügger also explained that pharmacists will be a critical component of future clinical studies to validate and further understand these biomarkers that can assist with determining cardiovascular risk.³

“We need clinical studies with the help of pharmacists to see if these markers can guide us, for example, for more intensive treatment,” Erdbrügger said.³

REFERENCES

1. Li X, Raisinghani N, Gallinat A, et al. Circulating extracellular vesicles in the pathogenesis of heart failure in patients with chronic kidney disease. Circulation. 2025;153(2). doi:10.1161/CIRCULATIONAHA.125.075579

2. Chronic kidney disease poisons patients’ hearts, scientists discover. News Release. University of Virginia Health System. Released January 20, 2026. Accessed January 21, 2026.

3. Interview with Uta Erdbrügger. Pharmacy Times. Retrieved January 22, 2026. Accessed January 22, 2026.