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Inflammation-Matrix Crosstalk in Vesicoureteral Reflux: Serum and Urinary ECM-Related Biomarkers and Renal Scarring
Marija Ratković-Janković1,2, Jelena Bašić3, Tatjana Jevtović-Stoimenov3
1Department of Pediatrics, Faculty of Medicine, University of Niš, 18000 Niš, Serbia.
Insights
Urinary extracellular matrix (ECM) biomarkers like TIMP-1 and TGF-β may indicate kidney damage in pediatric vesicoureteral reflux (VUR). Higher levels correlate with severe VUR and renal scarring, suggesting potential diagnostic value.
Area of Science:
- Nephrology
- Pediatric Urology
- Biomarker Research
Background:
- Vesicoureteral reflux (VUR) is a common condition in children, increasing the risk of urinary tract infections and renal scarring.
- Extracellular matrix (ECM) remodeling plays a role in kidney damage, but specific biomarkers for VUR are not well-established.
- Identifying reliable biomarkers can aid in assessing VUR severity and predicting renal outcomes.
Purpose of the Study:
- To evaluate serum and urinary ECM-related biomarkers in pediatric VUR patients.
- To determine the association of these biomarkers with VUR severity and renal scarring.
- To explore the potential clinical utility of ECM biomarkers in VUR management.
Main Methods:
- Serum and urinary levels of MMP-9, TIMP-1, CD147, TGF-β, and MCP-1 were measured in children with VUR and controls.
- Urinary biomarker concentrations were normalized to creatinine.
- Statistical analyses and receiver operating characteristic (ROC) curves were used to assess biomarker levels and discriminative performance.
Main Results:
- Serum MCP-1 was elevated in VUR patients; other serum markers showed no significant difference.
- Urinary TIMP-1, TGF-β, and MCP-1 were elevated, while CD147 was reduced in VUR patients compared to controls.
- Elevated urinary MMP-9, TIMP-1, and MCP-1 correlated with high-grade VUR and bilateral renal scarring.
- Urinary TIMP-1/Cr, TGF-β/Cr, and CD147/Cr showed moderate discriminative ability for VUR.
Conclusions:
- Urinary ECM-related biomarkers reflect intrarenal inflammatory and fibrotic processes in pediatric VUR.
- Specific urinary biomarkers like TIMP-1 and TGF-β may serve as indicators of VUR severity and renal damage.
- Further validation in larger, longitudinal studies is necessary to establish the clinical applicability of these biomarkers.
Abstract:
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.
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