Looking to the future: Can biomarkers reveal what we cannot see today?

Aim: A biomarker is a measurable characteristic that indicates a biological or pathogenic process or a response to an intervention. In children with vesicoureteral reflux, the main concern is silent and irreversible loss of renal tissue. Reflux grade, imaging, and kidney function tests may not identify this risk before permanent damage occurs. Aim of this review is to examine whether blood and urinary biomarkers can identify clinically relevant reflux, active parenchymal injury, established scarring, or future adverse outcomes, and thereby support personalised management.Methods: PubMed/MEDLINE was searched for publications from 1 January 2016 to 21 July 2026. Earlier key studies and reference lists supplemented the search. Paediatric primary studies were prioritised, while systematic and narrative reviews provided context and identified additional evidence. Findings were synthesised by intended clinical use, biological pathway, target outcome, and methodological limitations.Results: Urinary neutrophil gelatinase-associated lipocalin (NGAL) is the most extensively studied candidate, but its pooled accuracy for detecting established renal scarring is moderate. Tubular, inflammatory, fibrotic, functional, and molecular markers may provide complementary information. Most studies, however, are small, cross-sectional, and single-centre. They distinguish existing scars more often than they predict future injury or differential benefit from treatment.Conclusions: Biomarkers may reflect biological activity that anatomy alone cannot show, but current evidence does not support replacing cystography or renal cortical scintigraphy. Future studies should evaluate longitudinal multimarker models that integrate urinary biomarkers with clinical and imaging data, and determine whether biomarker-guided decisions improve meaningful patient outcomes.