Inflammation–Matrix Crosstalk in Vesicoureteral Reflux: Serum and Urinary ECM-Related Biomarkers and Renal Scarring

This study evaluated serum and urinary extracellular matrix (ECM)-related biomarkers in pediatric patients with vesicoureteral reflux (VUR) and their association with disease severity and renal scarring. Children with VUR and control subjects were included. Serum and urinary concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD147, transforming growth factor-β (TGF-β), and monocyte chemoattractant protein-1 (MCP-1) were analyzed, with urinary values normalized to creatinine. Serum MCP-1 levels were higher in patients with VUR (p < 0.001), whereas other serum biomarkers showed no significant differences. Creatinine-normalized urinary TIMP-1 and TGF-β levels were significantly elevated (p = 0.006 and p = 0.008, respectively), while CD147 levels were reduced (p = 0.011) in VUR patients. Receiver operating characteristic analysis demonstrated moderate discriminative performance for uTIMP-1/Cr (AUC = 0.74), uTGF-β/Cr (AUC = 0.73), and uCD147/Cr (AUC = 0.72). Higher urinary levels of MMP-9 (p = 0.014), TIMP-1 (p = 0.003), and MCP-1 (p = 0.015) were associated with high-grade VUR and with bilateral renal scarring (p = 0.048, p = 0.041, and p = 0.025, respectively). These findings suggest that urinary ECM-related biomarkers may reflect intrarenal inflammatory and fibrotic processes in VUR. However, their clinical applicability remains limited and requires validation in larger, longitudinal studies.