Urinary proteome analysis to exclude severe vesicoureteral reflux

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.