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Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study
Alev Yilmaz1,2, Alberto Caldas Afonso3, Ipek Akil4
1Division of Pediatric Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye. alev.yilmaz@istanbul.edu.tr.
Insights
Urinary heat shock protein 70 (uHSP70) accurately identifies urinary tract infections (UTI) in children. This novel marker can help avoid unnecessary antibiotic use in suspected UTI cases.
Area of Science:
- Pediatric infectious diseases
- Biomarker discovery
- Diagnostic accuracy studies
Background:
- Conventional urinalysis has limited accuracy in diagnosing pediatric urinary tract infections (UTI).
- This diagnostic challenge leads to frequent, unnecessary antibiotic prescriptions in children.
- Urinary heat shock protein 70 (uHSP70) is a potential new marker for acute urinary tract inflammation.
Purpose of the Study:
- To evaluate the added diagnostic value of uHSP70 in distinguishing UTI from other conditions in children.
- To assess the performance of uHSP70 compared to conventional urinalysis markers.
Main Methods:
- A multinational study involving 802 children across 37 pediatric centers.
- Urine and serum HSP70 levels were measured in children with confirmed UTI, non-UTI infections, contaminated samples, asymptomatic bacteriuria, and healthy controls.
- Statistical analysis was performed to determine sensitivity, specificity, and AUC for uHSP70 in diagnosing UTI.
Main Results:
- Urinary HSP70 was significantly elevated in children with UTI compared to all other groups (p < 0.0001).
- uHSP70 demonstrated high diagnostic accuracy for UTI, with 89% sensitivity and 82% specificity (AUC = 0.934).
- A threshold of uHSP70 > 48 ng/mL identified confirmed UTI with 90% sensitivity and 82% specificity, outperforming traditional urinalysis markers.
Conclusions:
- Urinary HSP70 is a novel, non-invasive biomarker that enhances the diagnostic accuracy of urinalysis for pediatric UTI.
- Implementing uHSP70 screening could potentially reduce empiric antibiotic administration by up to 80% in children with suspected UTI.
- Serum HSP70 levels were not found to be predictive of UTI.
Background:
The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI.
Methods:
A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI.
Results:
Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive.
Conclusions:
Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.
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