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Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic
Hsin-Hsiao S Wang1, Patricia S Cho2, Hui Zhi1
1Department of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
Insights
A novel urinary biomarker model combining MMP-7 and TIMP-2 can predict reduced renal function in patients with ureteropelvic junction obstruction (UPJO). This non-invasive tool aids in surgical decision-making for UPJO management.
Area of Science:
- Urology
- Biomarkers
- Renal Function
Background:
- Extracellular matrix proteins and degradation enzymes are linked to tissue fibrosis and ureteropelvic junction obstruction (UPJO).
- Identifying reduced renal function in UPJO patients is crucial for surgical decision-making.
Purpose of the Study:
- To develop a predictive urinary biomarker model for identifying UPJO patients at risk of reduced renal function.
- To establish a non-invasive method for assessing renal function in UPJO.
Main Methods:
- Prospective cohort study involving UPJO patients undergoing pyeloplasty.
- Measurement of urinary matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pre-operative urine samples.
- Development and validation of a multivariable logistic regression model to predict reduced renal function (MAG3 function <40%).
Main Results:
- The combined MMP-7 and TIMP-2 model demonstrated good predictive performance in both training (AUC = 0.830) and testing (AUC = 0.738) cohorts.
- Univariate analysis showed associations between reduced renal function and higher MMP-2, MMP-7, NGAL, and lower TIMP-2.
- The model effectively identified patients with reduced renal function, enabling risk stratification.
Conclusions:
- Urinary MMP-7 and TIMP-2 levels can effectively identify reduced renal function in UPJO patients.
- This biomarker combination offers a non-invasive approach to enhance surgical decision-making.
- Patients can be categorized into high-risk (aggressive management) or lower-risk (observation) groups based on biomarker levels.
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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