Vesicoureteral reflux (VUR) in children may lead to the renal
fibrosis and
scarring due to the overproduction and accumulation of
extracellular matrix proteins (ECM) in interstitial tissue.
Metalloproteinases produced in the kidneys are called
biological markers of
fibrosis. THE AIM OF THE STUDY was to assess if the presence of VUR in children disturb the balance between the serum and urinary concentrations of
matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 (TIMP-1) and 2 (TIMP-2) and predispose to excessive renal
fibrosis. MATERIAL AND METHODS. The study was performed in 88 children, median aged 5.5 years (0.08-16 yrs) with VUR confirmed by voiding cystouretrography (VCUG). In 95% of estimated children the
pyelonephritis indicated for VCUG performance. Control group consisted of 30 healthy children at similar age. Concentrations of MMP-2, MMP-9,
TIMP-1 and
TIMP-2 were estimated using immunoenzymatic ELISA method in urine of all examined children, additionally all the mentioned parameters in children with high (ll-V) grade of VUR were assessed in serum. RESULTS revealed that the urinary and serum concentrations of
TIMP-1 and
TIMP-2 were higher in healthy controls (p < 0.05). MMP-9 levels were higher only in the urine (p < 0.05) and MMP-2 in serum (p < 0.05). Increase in TIMP concentrations was connected with parallel increase in
MMP levels in children with I-V grades of VUR, what was confirmed by the normal values of
MMP-2/TIMP-2 and
MMP-9/TIMP-1 ratios (p > 0.05). Only children with Ill-rd grade of VUR revealed reduced values of
MMP/TIMP ratios (p < 0.05). Children's with Ill-V grade VUR revealed higher increase in serum concentrations of TIMP than in
MMP, it was also seen in decrease in
MMP/TIMP ratios (p < 0.05). No correlation was found between serum and urinary results of estimated parameters (p > 0.05).
CONCLUSION: MMP-2 and MMP-9 and
TIMP-1 and
TIMP-2 play role in pathogenesis of VUR disturbances, what was confirmed by the change in their serum and urinary concentrations. In serum and urine of children with high (Ill-V) grade VUR the biggest disturbances were observed in
MMPs: TIMPs system with the TIMP levels higher than
MMP values, what indirectly indicated ECM degradation disturbances and increase in renal
fibrosis.