Urinary extracellular vesicles: Potential biomarkers for vesicoureteral reflux

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Vesicoureteral reflux (VUR) is characterized by the backward flow of urine from the bladder to the upper urinary tract, causing kidney damage if left untreated. However, the current diagnostic method, voiding cystourethrography (VCUG), is invasive, potentially risky, and may cause anxiety, especially for young patients and their caregivers. Urinary extracellular vesicles (uEVs) are small vesicles originating from the renal tubular system that carry lipids, proteins, and RNAs for intercellular communication and regulation. uEVs have emerged as promising human biofluid-derived biomarkers in various kidney diseases. This chapter explores the potential of uEVs as noninvasive biomarkers for diagnosing VUR, monitoring its progression, and determining the extent of kidney damage. Previously, serum inflammatory markers have been identified as factors associated with kidney fibrosis in reflux nephropathy, but these may simply be a reflection of systemic inflammation rather than of a specific condition. Meanwhile, current research on uEVs in VUR remains limited. One study has identified vitronectin, a uEV-derived protein, as a predictor of VUR induced by spinal cord injury (sensitivity = 80%, specificity = 82.9%, area under the curve (AUC) = 0.795). Another study, focusing on pediatric VUR, showed that patients with kidney fibrosis had significantly higher urinary neutrophil gelatinaseassociated lipocalin (uNGAL) values than those without kidney fibrosis (1.49 ng/mL vs. 0.58 ng/mL, p < 0.001). However, apart from kidney fibrosis, uNGAL also increases in the contexts of AKI and pediatric urinary tract infections, indicating that uNGAL is not specific as a single marker for VUR. These findings highlight the importance of identifying biomarkers derived from entities, such as uEVs, that are specific to the urinary system and are not affected by systemic factors In summary, uEVs offer crucial insights into urinary tract processes and have broad potential for diagnosing, treating, and forecasting kidney and urinary tract diseases, including VUR. Future studies to test their role should encompass larger sample sizes, standardized protocols, and rigorous validation.

Original languageEnglish
Title of host publicationVesicoureteral Reflux
Subtitle of host publicationFrom Diagnosis to Treatment
PublisherNova Science Publishers, Inc.
Number of pages31
ISBN (Electronic)9798891135055
ISBN (Print)9798891134447
Publication statusPublished - 6 Feb 2024


  • Diagnostic
  • Fibrosis
  • Invasive
  • Kidney damage
  • Urinary tract


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