The role of urinary TIMP1 and MMP9 levels in predicting vesicoureteral reflux in neonates with antenatal hydronephrosis.

Background: Antenatal hydronephrosis (AH) is commonly found on evaluation of pregnant women and 20-30 % of neonates have vesicoureteral reflux (VUR). In order to diagnose VUR, we required invasive testing and exposure of the neonate to radiation. The concentrations of a matrix metalloproteinase, MMP9, and its inhibitor TIMP1, were analyzed in hydronephrotic newborns with VUR and were compared to those without reflux.

Methods: The neonates with a history of prenatal hydronephrosis were enrolled in two groups based on imaging study results, the neonates with VUR and without VUR. Neonates with a normal prenatal history and postnatal ultrasound were placed in a third group. We measured the random urinary levels of MMP9, TIMP1, and creatinine, their cut-off values and the MMP9/Cr and MMP9/TIMP1/Cr ratio was calculated, and an ROC curve was drawn.

Results: Sixty-nine neonates were enrolled in three groups; 27 patients (20 male, seven female) with AH and VUR were in group 1, 23 neonates (19 male, four female) without VUR were placed in group 2, and 19 (15 male, four female) acted as controls in group 3. The differences between the three groups and the normal and total hydronephrotic groups were statistically significant for MMP9, the MMP9/Cr, MMP9/TIMP1, and MMP9/TIMP1/Cr ratios. The urinary TIMP1 and TIMP1/Cr ratios were not significantly different between the groups. A cut-off value of MMP9 was measured as 358.5 ng/ml (sensitivity [sens] 74 %, specificity [spec] 78 %) and was used to compare groups 1 and 2. For groups 2 and 3, this cut-off was 181.00 pg/ml (sens 91 %, spec 89 %). The cut-off values measured for the MMP9/TIMP1 ratio were 30.32 (sens 70 %, spec 61 %) and 9.85 (sens 96 %, spec 89 %) to compare groups 1 and 2, and 2 and 3, respectively. We found no valuable cut-offs for the TIMP1 and TIMP1/Cr values. There was no difference between neonates with mild, moderate, and severe VUR according to urinary biomarker concentrations.

Conclusions: Evaluation of urinary levels of MMP9, or the MMP9/Cr, MMP9/TIMP1, or MMP9/TIMP1/Cr ratios may help us to differentiate the newborns with hydronephrosis and VUR from those without reflux.