[Serum and urinary concentration of selected metalloproteinases and their tissue inhibitors in children with vesicoureteral reflux]

Abstract

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.