Loading...
Thumbnail Image
Publication

Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction

Wang, Hsin-Hsiao S
Cho, Patricia S
Zhi, Hui
Kostel, Stephen A
DiMartino, Shannon
Dagher, Adelle M
Davis, Kylie H
Cabour, Lily D
Shimmel, Ashley
Lee, James
... show 4 more
Embargo Expiration Date
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).

Source

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. Association between urinary biomarkers MMP-7/TIMP-2 and reduced renal function in children with ureteropelvic junction obstruction. PLoS One. 2022 Jul 14;17(7):e0270018. doi: 10.1371/journal.pone.0270018. PMID: 35834547; PMCID: PMC9282603.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1371/journal.pone.0270018
PubMed ID
35834547
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Copyright: © 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Attribution 4.0 International