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  • Title: Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction.
    Author: Wang HS, Cho PS, Zhi H, Kostel SA, DiMartino S, Dagher AM, Davis KH, Cabour LD, Shimmel A, Lee J, Froehlich JW, Zurakowski D, Moses MA, Lee RS.
    Journal: PLoS One; 2022; 17(7):e0270018. PubMed ID: 35834547.
    Abstract:
    IMPORTANCE: Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-invasive way to enhance surgical decision making for patients and urologists. OBJECTIVE: We sought to develop a predictive model to identify UPJO patients at risk for reduced renal function. DESIGN: Prospective cohort study. SETTING: Pre-operative urine samples were collected in a prospectively enrolled UPJO biomarker registry at our institution. Urinary MMP-2, MMP-7, TIMP-2, and NGAL were measured as well as clinical characteristics including hydronephrosis grade, differential renal function, t1/2, and UPJO etiology. PARTICIPANTS: Children who underwent pyeloplasty for UPJO. MAIN OUTCOME MEASUREMENT: Primary outcome was reduced renal function defined as MAG3 function <40%. Multivariable logistic regression was applied to identify the independent predictive biomarkers in the original Training cohort. Model validation and generalizability were evaluated in a new UPJO Testing cohort. RESULTS: We included 71 patients with UPJO in the original training cohort and 39 in the validation cohort. Median age was 3.3 years (70% male). By univariate analysis, reduced renal function was associated with higher MMP-2 (p = 0.064), MMP-7 (p = 0.047), NGAL (p = 0.001), and lower TIMP-2 (p = 0.033). Combining MMP-7 with TIMP-2, the multivariable logistic regression model predicted reduced renal function with good performance (AUC = 0.830; 95% CI: 0.722-0.938). The independent testing dataset validated the results with good predictive performance (AUC = 0.738). CONCLUSIONS AND RELEVANCE: Combination of urinary MMP-7 and TIMP-2 can identify reduced renal function in UPJO patients. With the high sensitivity cutoffs, patients can be categorized into high risk (aggressive management) versus lower risk (observation).
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