The role of urinary biomarkers in the assessment of ureteropelvic junction obstruction

Abstract

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is an important cause of urinary tract obstruction and can lead to progressive deterioration of renal function. Thus the development of novel non-invasive methods capable of discriminating obstruction and hydronephrosis may be useful. Elevation of urinary biomarkers may provide early evidence of kidney damage in urinary biomarkers may provide early evidence of kidney damage in urinary obstruction. In this scenario, urinary concentrations of kidney injurymolecule-1 (KIM-1) may be elevated following proximal tubular injury, while neutrophil gelatinase-associated lipocalin(NGAL), may increase as result of injury to proximal or distal tubule as well as to loop of Henle, CA19-9 after overproduction in the obstructed tubules and ²2 microglobulin (²2M) after injury to the glomerulus or the proximal tubule. Extracellular matrix (ECM) metabolism might be also involved in the pathophysiology of UPJO. Some studies have already shown abnormalities in the ECM components: smooth muscle, collagen composition and innervation pattern. Our group showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in the obstructed ureteropelvic junction (UPJ) tissue. The gelatinase (Matrix metalloproteinases 9, MMP9) degrades the type IV collagen of the basal membrane. TIMP-1 is a specific inhibitors of MMP9. We propose that urinary concentration of MMP9 may be elevated and TIMP-1 may diminished in patients with UPJO, reflecting what was previously shown in UPJ tissue. Transforminggrowthfactor²1 (TGF-²1) is a multifunctionalcytokine crucial for embryonicdevelopmentand for repair and regeneration after tissue injury. Increasing pressure in the renal pelvis stimulates the renin-angiotensin system (RAS), which, in turn, stimulates the expression of TGF-²1. Transforming growth factor ²1 is detectable in the urine of patients with pathological conditions of the urinary tract. Monocyte chemoattractant protein-1(MCP-1), is a powerful and specific chemotactic and activating factor for monocytes/macrophagesand T lymphocytes, has been proposed as a possible mediator of tubule interstitial lesions that follow endocytosis off iltered proteins. It is expressed by tubular epithelial cells, infiltrating monocytes, lymphocytes, and peritubular capillary endothelial cells in different renal diseases suggesting a link between the inflammatory response and tubular function. There is a possibility of direct involvement in the progression of renal damage in UPJO.OBJECTIVEThe aim of this study is to evaluate the diagnostic properties of these urinary biomarkers, correlate such values to predict surgical indication or clinical follow-up.METHODSA prospective study on consecutive patients with UPJO.We will divide them into three groups: I) hydronephrosis needing surgical intervention (30 pts), non progressive hydronephrosis (follow-up group: 20 pts) and a control group consisting of patients without obstruction will be submitted to urinary markers collection (age-matched patients submitted to circumcision or orchiopexy; 30 pts). The following surgical indications will be considered: hydronephrotic kidney with renal impairment estimated by radioisotopic exams; ipsilateral flank pain; previous episodes of pyelonephritis; complications related to UPJO: lithiasis, hypertension, hematuria. Exclusion criteria included patients with bilateral UPJO, unilateral UPJO with contralateral pathologic kidney, solicitary kidney, history of previous surgical treatment for UPJO or glomerular filtration rate below 60ml/min/1,73m2. Each patient of the group with UPJO and surgical indication wil provide four voided urine samples for biomarker measurement, one at preoperative consultation and the others at 1, 3 and 6 months of postoperative follow-up. Patients with UPJO in the follow-up group will provide two voided urine sample with interval of 6 months and controls will provide only one voided urine sample. (AU)