ABSTRACT
BACKGROUND: Ureteropelvic junction obstruction (UPJO) diagnosed prenatally occurs in 1:150 - 1:1200 pregnancies. Although many studies investigating the molecular changes of this obstructed segment have been performed, the underlying mechanisms are still unclear. The role of extracellular matrix (ECM) components remains controversial, and the investigations in the field of ECM changes, might help the better understanding of the pathogenesis of this common condition. The aim of the present study was to investigate for the first time in the literature whether MMP9 and its specific inhibitors, TIMP1 and RECK, are expressed in a reproducible, specific pattern in UPJ. METHODS: UPJO specimens were obtained from 16 children at the time of dismembered pyeloplasty due to intrinsic UPJ stenosis. Expression levels of the three genes (MMP9, TIMP1 and RECK) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Then correlated the expression levels of the genes according to grade study population that was divided in 2 categories according to Society of Fetal Urology classification, grade 3 (moderate) and 4 (severe). For DTPA we subdivided the childrens in 2 groups, obstructive (T 1/2 more than 20 min) and partial obstructive (T 1/2 between 10 and 20 min) and success in a surgery was defined as decrease in T 1/2 to less than 20 min, absence of symptoms, improving renal function and decreasing dilatation on successive exams. RESULTS: MMP9 was underexpressed and TIMP1 and RECK were overexpressed in children with obstructive DTPA but the differences were not statistically significant. Overexpression of MMP9 was higher among patients with severe grade of UPJ compared to those with moderate grade. Surprisingly expression levels of MMP-9 was three times higher in children who were successfully treated by surgery (n = 10) (p = 0.072), so those who were followed for at least 1 year after surgery and remained with improvement in renal function and decreasing dilation on intravenous urogram and TIMP-1 was underexpressed in 100 % of this cases (p = 0.00). CONCLUSIONS: We showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in children who improving renal function and decreasing dilation after surgery. We believe that the higher expression of MMP9 in these cases can reflect an increase in degradation and remodeling process that could be used as a marker for surgical outcome.
Subject(s)
GPI-Linked Proteins/biosynthesis , Kidney Pelvis , Matrix Metalloproteinase 9/biosynthesis , Tissue Inhibitor of Metalloproteinase-1/biosynthesis , Ureteral Obstruction/surgery , Adolescent , Child , Child, Preschool , Female , GPI-Linked Proteins/genetics , Gene Expression Regulation , Humans , Infant , Male , Matrix Metalloproteinase 9/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Treatment Outcome , Ureteral Obstruction/geneticsABSTRACT
PURPOSE: In this study we evaluate the diagnostic accuracy of renal pelvic dilatation for detecting infants with prenatal hydronephrosis who will need surgical intervention for ureteropelvic junction obstruction during followup. MATERIALS AND METHODS: Between 1999 and 2010, 371 newborns diagnosed with isolated prenatal hydronephrosis were prospectively followed. The main event of interest was the need for pyeloplasty. Diagnostic odds ratio, sensitivity, specificity and diagnostic accuracy (assessed by AUC) of fetal renal pelvic dilatation and postnatal renal pelvic dilatation were evaluated. RESULTS: A total of 312 patients were included in the analysis and 25 (7.5%) infants underwent pyeloplasty. The diagnostic performance for detecting the need for pyeloplasty was excellent for all ultrasonography measurements. The AUC was 0.96 (95% CI 0.92-0.98) for fetal renal pelvic dilatation, 0.97 (95% CI 0.95-0.98) for postnatal renal pelvic dilatation and 0.95 (95% CI 0.92-0.97) for the Society for Fetal Urology grading system. A cutoff of 18 mm for fetal renal pelvic dilatation and a cutoff of 16 mm for postnatal renal pelvic dilatation had the best diagnostic odds ratio to identify infants who needed pyeloplasty. Considering a diagnosis to be positive only if fetal renal pelvic dilatation was greater than 18 mm and postnatal dilatation was greater than 16 mm, sensitivity was 100% and specificity was 86% (95% CI 80.7-89.9). CONCLUSIONS: Our findings suggest that the combination of fetal and postnatal renal pelvic dilatation is able to increase the diagnostic accuracy for detecting infants who need a more comprehensive postnatal investigation for upper urinary tract obstruction.