Institute of Science Tokyo develops microRNA-based method to predict CKD and cardiovascular risk

A research team led by Associate Professor Shintaro Mandai (tenure track), Doctoral Student Shunsuke Inaba (third-year), and Professor Shinichi Uchida from the Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, in collaboration with Associate Professor Takanori Hasegawa from the M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo, has developed a new technology to predict the long-term risk of onset and progression of chronic kidney disease (CKD) and cardiovascular complications. Going forward, the team aims to translate this technology into a risk score that can be routinely applied in clinical settings, with the goal of improving prognosis for CKD patients. Their findings were published in JAHA: Journal of the American Heart Association.

The number of CKD patients in Japan is estimated to exceed 20 million. Because CKD affects not only the kidneys but also the cardiovascular system and metabolism, these conditions are collectively referred to as cardiovascular-kidney-metabolic (CKM) syndrome. However, reliable indicators and molecular mechanisms for accurately predicting disease progression and long-term risk of cardiovascular complications have not yet been sufficiently established.

The research team comprehensively analyzed the levels of microRNAs (miRNAs) encapsulated in circulating extracellular vesicles (cEVs) in the blood of a cohort of 36 CKD patients. There are more than one billion EVs per milliliter of blood, and they transport messenger molecules between cells. Furthermore, the team used machine learning algorithms to extract miRNAs associated with CKD and cardiovascular complications.

As a result, the depletion of certain miRNA groups was found to be associated with increased risk of CKD and cardiovascular complications. A predictive model combining three of these miRNAs demonstrated unprecedentedly high predictive accuracy.

Further analysis of each of these three miRNAs found that patients with depleted levels showed a higher prevalence of complications involving not only the kidneys but also the cardiovascular and metabolic systems throughout the body. For example, these patients had a history of cardiovascular disease (CVD), complications of hypertension, used diuretics, antihypertensives, and antidiabetic medications, and needed to receive anemia treatment.

The miRNA profiles reflect the function of EVs and may be deeply involved in the pathophysiology of cardiorenal-metabolic syndrome. These miRNAs show potential not only as new molecular markers for CKM syndrome but also as a pathway to elucidating disease mechanisms.

Going forward, the team will conduct large-scale intervention trials based on patient stratification using the predictive model and will verify whether treatment interventions guided by risk scores improve clinical outcomes. The ultimate goal is to put this into practical use as a risk score that can be routinely applied in clinical settings. Additionally, by clarifying the biological mechanisms, they aim to establish the foundation for novel therapeutic strategies, including miRNA supplementation and restoration of circulating EV function.

Journal Information
Publication: Journal of the American Heart Association
Title: Circulating Extracellular Vesicle MicroRNAs as Predictive Biomarkers for Kidney and Cardiovascular Events
DOI: 10.1161/JAHA.125.045148