Urinary extracellular matrix proteins as predictors of the severity of ureteropelvic junction obstruction in children

Abstract

Introduction Ureteropelvic junction obstruction (UPJO) particu-larly represents a challenge in regard to manage-ment, as not all hydronephrosis (HN) represent a kidney-damaging state. Urinary biomarkers have been proposed as noninvasive tools. Extracellular matrix (ECM) proteins are associated with tissue fibrosis in the setting of UPJO and is poorly explored. Objective To investigate whether urinary ECM proteins are useful to discriminate the severity of urinary obstruction on unilateral UPJO. Study design Children with unilateral UPJO were prospective enrolled. Urinary (u) matrix metalloproteinases (MMP-1,-2,-9 and TIMP-1,-2) as well as clinical characteristics were measured in the following groups: 26 children with obstructive HN at initial diagnosis and after six months of dismembered pyeloplasty; 22 children with non-obstructive HN at diagnosis and after six months of observation; 26 children without any urinary tract condition, as the control group. Results were assessed statistically using for homogenous groups, a one-way analysis of variances (ANOVA) and for nonparametric groups, Mann-Whitney test or Kruskal-Wallis test was per -formed. ROC curves were performed. Results Baseline samples demonstrated a higher concentra-tion of uMMP-1/Cr, uMMP-2/Cr, u-TIMP-1/Cr and u-TIMP-2/Cr in obstructive HN group; uMMP-9/Cr levels were higher in non-obstructive HN group and all studied biomarkers had lower concentrations for the control group. On follow-up, for the obstructive HN group, urinary concentration of uTIMP-1/Cr and uTIMP-2/Cr decreased, and uMMP-1/Cr, uMMP-2/Cr and uMMP-9/Cr increased when comparing preop-erative to postoperative values. In the non-obstructive HN group, all proteins analyzed were stable after six months of observation. ROC curves analysis showed a promising diagnostic profile for the detection of obstructive HN for uTIMP-1/Cr (area under the curve-AUC-; of 0.692), uTIMP-2/Cr (AUC of 0.678) and for uMMP-2/Cr (AUC of 0.655). Discussion The severity of kidney obstruction could correlate with the urinary ECM proteins concentration in this study. This is concordant with prior studies demon-strating that a disruption of the balance of accu-mulation/degradation of the ECM proteins occur on obstructive uropathy. Limitations of our study include the older age of our patients and that these markers had no influence at all on the surgical decision. Conclusion We demonstrate that obstructive HN have signifi-cantly higher uMMP-2, uTIMP-1 and uTIMP-2 con-centrations. Particularly, uTIMP-2 levels were correlated to severity of obstruction and therefore, it might be a useful urinary biomarker to correctly allocate children with HN between surgical man-agement vs follow-up. After pyeloplasty, uTIMP-1 and uTIMP-2 presented a progressive decrease postoperatively, which is also highly desirable for urinary markers.