Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection

Turk J Urol. 2017 Dec;43(4):536-542. doi: 10.5152/tud.2017.06337. Epub 2017 Dec 1.

Abstract

Objective: Urinary tract infection occurs in 1.8-6.6% of children under 6 years old. The aim of this study was to assess the urinary concentrations of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1), in children with acute pyelonephritis (APN) and the potential to develop renal scarring.

Material and methods: Children who had experienced an episode of APN were divided into 2 groups. Group 1 included children with APN who exhibited scarring and group 2 included children with APN who had a normal 99mTechnetium dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in the acute phase of infection. A receiver operating characteristic curve was generated to allow calculation of cut-off values.

Results: Sixty-one children were enrolled across the 2 groups: group 1 contained 16 patients (all female); group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1 were significantly higher in group 1 than in group 2 (p=0.037 and 0.022 respectively). For comparison of groups 1 and 2, the cut-off values were measured as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value, PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%, specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75% specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9×TIMP1 levels, respectively.

Conclusion: Evaluation of urinary MMP9 and TIMP1 levels may help to identify children with APN who are at risk of developing renal scarring.

Keywords: Children; matrix metalloproteinase; pyelonephritis; tissue inhibitor of metalloproteinase 1; urinary tract infection; vesico-ureteral reflux.