Urinary excretion of EGF and MCP-1 in children with vesico-ureteral reflux

Abstract

Purpose The aim of this study was to investigate the urinary concentration of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) as reflux nephropathy (RN) biomarkers before and after endoscopic treatment of moderate to severe vesico-ureteral reflux (VUR).Materials and methods A prospective study was carried out on 72 children with moderate to severe VUR. All patients underwent endoscopic treatment using Macroplastique® or Deflux®. Vesico-ureteral reflux resolution was tested by post-operative voiding cystourethrography after 3 months and 2 years. Follow-up urinary samples were collected at that time. Control samples were taken from healthy children with no clinical evidence of renal and bladder disease and no history of UTI.Results In VUR patients, pre-operative urinary EGF levels had a down-regulation when compared to controls. Following successful VUR repair, urinary EGF levels of VUR children progressively increased only at long term follow-up but without returning to normal levels. Urinary MCP-1 levels were highly expressed in pre-operative samples and decreased markedly during early post-operative measurements. Urinary MCP-1 levels did not further decreased in late post-operative follow-up. In fact, these levels remained significantly higher when compared to controls.Conclusions Urinary levels of EGF and MCP-1 may become useful markers for monitoring the response to surgical treatment in VUR patients. Although endoscopic VUR treatment is effective in reducing the inflammatory response, the persistence of significant abnormal levels of inflammatory cytokines (such as urinary MCP-1) at long term follow-up suggests that surgery alone may not completely treat the chronic renal inflammation evidenced in these children.

Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT

“…15 Furthermore, it has been demonstrated that EGF, MCP-1 (plus their ratio EGF/MCP-1), and β2M may be used as possible indicators of progressive renal damage and recovery in children with urinary tract obstruction 3,6,16 and VUR. 17 Similar findings in obstructive nephropathy patients have been observed by other authors. 18 The separate monitoring of these urinary biomarkers may not be indicative of an ongoing process occurring in renal parenchyma, 19 which is most likely influenced by the interaction of MCP-1 and EGF so we studied also uEGF/uMCP-1 and uEGF/u β2M ratios.…”

“…We have shown that urinary tract obstruction and VUR are associated with increased urinary excretion of MCP-1. [6][7][8]17 Then, the presence of associated conditions such as urinary tract obstruction and vesicoureteral in hypoplastic, agenetic, and multicystic groups justified itself the increased urine excretion of MCP-1/Creat in those patients.…”

Role of urinary transforming growth factor beta-b1 and monocyte chemotactic protein-1 as prognostic biomarkers in posterior urethral valve

“…Similar assay results were found in other studies having higher levels of MCP1 in pediatric obstructive uropathy and reflux nephropathy. [ 14 15 16 ]…”