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Updated: Dec 31, 2025

Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis
Published on: May 8, 2021
Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the
Dijana Vitko1, Patricia S Cho2, Stephen A Kostel1
1Department of Urology, Boston Children's Hospital, Boston, Massachusetts.
Insights
Children with recurrent urinary tract infections (UTIs) and vesicoureteral reflux (VUR) show altered urinary proteomes. These changes in inflammation and metabolism proteins may indicate infection risk and potential kidney damage.
Area of Science:
- Biochemistry
- Pediatric Nephrology
- Proteomics
Background:
- Recurrent urinary tract infections (UTIs) are a significant health concern, particularly in children.
- The underlying mechanisms and urinary proteome changes in children predisposed to UTIs, especially those with vesicoureteral reflux (VUR), are not fully understood.
- Identifying UTI risk factors is crucial for managing VUR and preventing infection-related renal damage.
Purpose of the Study:
- To investigate the urinary proteome differences in children with VUR and recurrent UTIs.
- To identify specific urinary proteins associated with risk factors for UTIs and renal scarring in pediatric VUR patients.
Main Methods:
- Urinary proteomes of 22 children with low-grade VUR, recurrent UTIs, and renal scarring were compared to 22 age-matched controls.
- Mass spectrometry was used for urinary protein analysis, with quantitation based on spectral counting.
- Differential protein expression was assessed using statistical analysis (q <0.075, FC ≥1.2).
Main Results:
- A total of 2,551 proteins were identified, with 964 robustly quantified.
- Eighty proteins showed differential expression between the VUR and control groups (44 up-regulated, 36 down-regulated).
- Altered urinary proteins were associated with inflammation, acute phase response (APR), extracellular matrix (ECM) modulation, and carbohydrate metabolism.
Conclusions:
- The urinary proteome is significantly altered in children with VUR and recurrent UTIs.
- Specific protein alterations may serve as biomarkers for UTI risk and potential renal damage in this population.
- Further research into these proteomic changes could improve diagnostic tools and clinical management strategies for pediatric VUR.
Abstract:
Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.
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