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Updated: May 25, 2026

Proteomic Profile of EPS-Urine through FASP Digestion and Data-Independent Analysis
Published on: May 8, 2021
Urinary proteome analysis to exclude severe vesicoureteral reflux
Jens Drube1, Eric Schiffer, Esther Lau
1Clinic of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. jens.drube@web.de
Insights
A new noninvasive urinary proteome test accurately identifies high-grade vesicoureteral reflux (VUR) in children with urinary tract infections (UTI). This test can help avoid unnecessary invasive diagnostics for most children.
Area of Science:
- Urology
- Pediatric Nephrology
- Biomarker Discovery
Background:
- High-grade vesicoureteral reflux (VUR) (grade IV-V) is a significant risk factor for renal scarring, impaired kidney function, and hypertension.
- Current gold standard for VUR diagnosis, voiding cystourethrography (VCUG), is invasive.
- Most children with urinary tract infection (UTI) do not have high-grade VUR, leading to unnecessary invasive procedures.
Purpose of the Study:
- To develop and validate a noninvasive diagnostic test for identifying high-grade VUR in children.
- To reduce the need for invasive diagnostics in the majority of children presenting with UTI.
Main Methods:
- A case-control study utilized capillary electrophoresis coupled to mass spectrometry to establish a urinary proteome pattern.
- The proteome pattern distinguished 18 children with VUR grade IV-V from 19 controls without VUR after UTI.
- Independent validation was performed in a blinded cohort of 17 VUR patients and 19 controls.
Main Results:
- The noninvasive test demonstrated 88% sensitivity and 79% specificity for detecting VUR grade IV-V in the blinded cohort.
- Test accuracy was independent of patient age, gender, and contralateral kidney VUR grade.
- A positive test result yielded an odds ratio of 28 for having high-grade VUR.
Conclusions:
- A novel noninvasive urinary proteome test shows promise for identifying high-grade VUR in children with UTI.
- This test is ready for prospective validation in larger cohorts.
- The test could spare children without pathological proteome patterns from further invasive diagnostics like VCUG.
Objectives:
High-grade vesicoureteral reflux (VUR, grade IV or V) is a risk factor for renal scarring, impaired renal function, and arterial hypertension. Voiding cystourethrography is the gold standard for detecting the severity of VUR. High-grade VUR is present in the minority of children with urinary tract infection (UTI), thus exposing the majority to invasive diagnostics that have no surgical consequence. We therefore aimed at establishing a noninvasive test to identify children with high-grade VUR.
Methods:
In a case-control study, a specific urinary proteome pattern was established by capillary electrophoresis coupled to mass spectrometry in 18 patients with primary VUR grade IV or V, distinguishing these from 19 patients without VUR after UTI. This proteome pattern was independently validated in a blinded cohort of 17 patients with VUR grade IV or V and 19 patients without VUR.
Results:
Sensitivity in detecting VUR grade IV or V in the blinded study was 88%, specificity was 79%. The test's accuracy was independent of age, gender, and grade of VUR in the contralateral kidney. The odds ratio of suffering from VUR grade IV or V when tested positive was 28 (95% confidence interval: 4.5 to 176.0).
Conclusions:
This noninvasive test is ready for prospective validation in large cohorts with the aim of identifying those children with UTI and hydronephrosis in need of further invasive diagnostics, such as voiding cystourethrography, thus sparing most children without pathologic urinary proteome patterns from additional diagnostics.
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