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Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
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Circulating Extracellular Vesicle MicroRNAs as Predictive Biomarkers for Kidney and Cardiovascular Events.

Shunsuke Inaba1, Takanori Hasegawa2, Yuta Nakano1

  • 1Department of Nephrology, Graduate School of Medical and Dental Sciences Institute of Science Tokyo Tokyo Japan.

Journal of the American Heart Association
|December 10, 2025
PubMed
Summary

A new risk model using microRNAs from extracellular vesicles can predict adverse kidney and cardiovascular events in chronic kidney disease (CKD) patients noninvasively, improving early risk identification.

Keywords:
biomarkercardiovascular‐kidney‐metabolic syndromechronic kidney diseaseextracellular vesiclesmicroRNA

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Area of Science:

  • Biomarkers
  • Genomics
  • Cardiovascular Medicine

Background:

  • Chronic kidney disease (CKD) patients face high mortality from cardiovascular events.
  • Current predictive models for kidney and cardiovascular outcomes in CKD are insufficient.
  • CKD is associated with syndromes like cardiorenal anemia and cardiovascular-kidney-metabolic (CKM).

Purpose of the Study:

  • To develop a minimally invasive risk model for predicting kidney and cardiovascular outcomes in CKD patients.
  • To utilize circulating small extracellular vesicle-derived microRNAs (miRNAs) for risk prediction.
  • To improve early identification and clinical decision-making for CKD patients.

Main Methods:

  • Microarray-based miRNA profiling in a derivation cohort (n=36).
  • Development of a penalized Cox proportional hazards model.
  • Validation using quantitative polymerase chain reaction in a larger CKD cohort (n=234).

Main Results:

  • Twenty-three miRNAs were downregulated in advanced CKD, linked to senescence and cell cycle pathways.
  • A risk score was developed using three specific miRNAs (hsa-let-7d-5p, hsa-miR-24-3p, hsa-miR-126-3p), cystatin C, and urinary protein.
  • The model accurately predicted adverse kidney and cardiovascular events, stratifying risk within CKM stages.

Conclusions:

  • Circulating small extracellular vesicle-derived miRNAs offer a noninvasive method for longitudinal risk prediction in CKD.
  • This miRNA-based model can enhance early risk identification and guide clinical decisions.
  • The findings support the use of extracellular vesicle miRNAs as valuable biomarkers in managing CKD and its complications.