Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

Abstract

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.

• Authors: Alev Yilmaz, Alberto Caldas Afonso, Ipek Akil, Bagdagul Aksu, Harika Alpay, Bahriye Atmis, Ozlem Aydog, Aysun Karabay Bayazıt, Meral Torun Bayram, Ilmay Bilge, Ipek Kaplan Bulut, Bahar Buyukkaragoz, Elif Comak, Belde Kasap Demir, Nida Dincel, Osman Donmez, Mehmet Akif Durmus, Hasan Dursun, Ruhan Dusunsel, Ali Duzova, Pelin Ertan, Asuman Gedikbasi, Nilufer Goknar, Sercin Guven, Duygu Hacihamdioglu, Augustina Jankauskiene, Mukaddes Kalyoncu, Salih Kavukcu, Bahriye Uzun Kenan, Nuran Kucuk, Bahar Kural, Mieczysław Litwin, Giovanni Montini, William Morello, Ahmet Nayir, Lukasz Obrycki, Beyhan Omer, Ebru Misirli Ozdemir, Nese Ozkayin, Dusan Paripovic, Cemile Pehlivanoglu, Seha Saygili, Susanne Schaefer, Ferah Sonmez, Yilmaz Tabel, Nesrin Tas, Mehmet Tasdemir, Ana Teixeira, Demet Tekcan, Sebahat Tulpar, Ozde Nisa Turkkan, Berfin Uysal, Metin Uysalol, Daiva Vaiciuniene, Sevgi Yavuz, Sibel Yel, Tarik Yildirim, Zeynep Yuruk Yildirim, Nurdan Yildiz, Selcuk Yuksel, Eray Yurtseven, Franz Schaefer, Rezan Topaloglu
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 38 Issue 3 Pg. 791-799 (03 2023) ISSN: 1432-198X [Electronic] Germany
• PMID: 35849222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.

Chemical References

• Anti-Bacterial Agents
• HSP70 Heat-Shock Proteins

Topics

• Humans
• Child
• Urinary Tract Infections (drug therapy)
• Urinalysis
• Anti-Bacterial Agents (therapeutic use)
• HSP70 Heat-Shock Proteins
• Urinary Tract
• Sensitivity and Specificity