5 Minutes
Breakthrough summary
A team at the Centre de recherche du CHUM (CRCHUM), affiliated with Université de Montréal, has identified a microRNA that both signals and preserves the tiny blood vessels crucial to kidney function. The molecule, miR-423-5p, emerged as a candidate blood-based biomarker for kidney microvascular health and, in preclinical models, helped protect peritubular capillaries after acute injury. Credit: Shutterstock
The finding could enable earlier detection of microvascular damage in people at risk of chronic kidney disease (CKD) and suggests new therapeutic strategies to limit long-term kidney decline after events such as transplant ischemia-reperfusion or other surgeries that temporarily interrupt blood flow.
Scientific background and discovery
MicroRNAs are short, non-coding RNA molecules that regulate gene expression and are detectable in blood. The CRCHUM team screened circulating microRNA levels in animal models and human samples and identified miR-423-5p as a reproducible indicator of microvascular status in injured kidneys. The work appears in JCI Insight and was led by Université de Montréal medical professors Marie-Josée Hébert and Héloïse Cardinal, with significant contributions from research associate Francis Migneault.
Dr. Marie-Josée Hébert (left) and Dr. Héloïse Cardinal (right), CRCHUM researchers and holders of the Shire Chair in Nephrology, Renal Transplantation and Regeneration, co-authored the study with Hébert’s research associate Francis Migneault (center). Credit: CHUM
Peritubular capillaries are microscopic vessels that surround kidney tubules and are essential for removing metabolic waste and delivering oxygen and nutrients. Loss or rarefaction of these capillaries is a hallmark of progressive CKD and correlates with long-term loss of renal function. Until now, clinicians has lacked a reliable circulating biomarker to assess this specific microvascular damage noninvasively.
Evidence: animal models and human transplant samples
The researchers first observed that circulating miR-423-5p levels varied in mice after experimentally induced acute kidney injury. Those preclinical observations were then validated using blood samples from 51 kidney transplant recipients available through the CHUM transplant biobank. Clinical correlations indicated that miR-423-5p measurements reflected the status of the kidney microvasculature and could track changes following interventions.
Importantly, therapeutic experiments in mice showed that administration of miR-423-5p after kidney injury preserved peritubular capillaries and reduced subsequent tissue damage. While direct injection into a graft during transplant is feasible in a surgical setting, systemic delivery and organ-targeting remain technical hurdles. The team is now exploring delivery platforms — including nanoparticle carriers, localized perfusion during transplant, or microRNA cocktails — to transport miR-423-5p effectively to the kidney in patients.
Clinical implications, broader applications and next steps
A validated blood test based on miR-423-5p could change perioperative monitoring and long-term management for higher-risk groups: transplant recipients, elderly patients, and people undergoing cardiovascular or vascular procedures where blood flow interruption is common. Early detection of microvascular deterioration would allow clinicians to adjust immunosuppression, perioperative care, or introduce targeted microvascular-protective therapies sooner.
Beyond nephrology, the investigators note potential relevance for other conditions where small-vessel loss contributes to disease, such as heart failure, pulmonary diseases, and certain neurodegenerative disorders associated with aging. Ongoing projects at CRCHUM, including work on pulmonary microvasculature, aim to test whether similar microRNA signatures apply across organs. The CHUM biobank also enables retrospective analyses to determine if commonly used medications given after transplant affect capillary health.
Expert Insight
Dr. Elena Park, a nephrology researcher unaffiliated with the study, comments: 'Identifying a circulating marker that reflects peritubular capillary health is an important step. If miR-423-5p validation holds in larger cohorts, it could be integrated into transplant and perioperative workflows. The therapeutic findings in mice are promising, but human delivery methods and safety will be key to clinical translation.'
Conclusion
The CRCHUM team's identification of miR-423-5p as both a biomarker and a protective agent for kidney microvessels marks a world-first advance in microvascular nephrology. The discovery offers a dual path: develop blood tests for earlier detection of microvascular injury and pursue targeted delivery approaches to preserve capillaries and slow progression to chronic kidney disease. Further validation in larger patient cohorts and the design of safe, organ-directed delivery systems will determine how quickly this scientific insight becomes a clinical tool.
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