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. 2023 Mar;38(3):791-799.
doi: 10.1007/s00467-022-05664-5. Epub 2022 Jul 18.

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

Alev Yilmaz  1   2 , Alberto Caldas Afonso  3 , Ipek Akil  4 , Bagdagul Aksu  5   6 , Harika Alpay  7 , Bahriye Atmis  8   9 , Ozlem Aydog  10 , Aysun Karabay Bayazıt  9 , Meral Torun Bayram  11 , Ilmay Bilge  12 , Ipek Kaplan Bulut  13 , Bahar Buyukkaragoz  14 , Elif Comak  15 , Belde Kasap Demir  16   17 , Nida Dincel  18 , Osman Donmez  19 , Mehmet Akif Durmus  20 , Hasan Dursun  21 , Ruhan Dusunsel  22 , Ali Duzova  23 , Pelin Ertan  4 , Asuman Gedikbasi  24 , Nilufer Goknar  25 , Sercin Guven  7 , Duygu Hacihamdioglu  26 , Augustina Jankauskiene  27 , Mukaddes Kalyoncu  28 , Salih Kavukcu  11 , Bahriye Uzun Kenan  14 , Nuran Kucuk  29 , Bahar Kural  30 , Mieczysław Litwin  31 , Giovanni Montini  32   33 , William Morello  32 , Ahmet Nayir  5   6 , Lukasz Obrycki  31 , Beyhan Omer  34 , Ebru Misirli Ozdemir  35 , Nese Ozkayin  36 , Dusan Paripovic  37 , Cemile Pehlivanoglu  38 , Seha Saygili  39 , Susanne Schaefer  40 , Ferah Sonmez  41 , Yilmaz Tabel  42 , Nesrin Tas  23 , Mehmet Tasdemir  12 , Ana Teixeira  3 , Demet Tekcan  10 , Sebahat Tulpar  43 , Ozde Nisa Turkkan  5 , Berfin Uysal  44   45 , Metin Uysalol  46 , Daiva Vaiciuniene  27 , Sevgi Yavuz  47 , Sibel Yel  22 , Tarik Yildirim  48 , Zeynep Yuruk Yildirim  5   6 , Nurdan Yildiz  7 , Selcuk Yuksel  49 , Eray Yurtseven  50 , Franz Schaefer  40 , Rezan Topaloglu  23
Affiliations

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

Alev Yilmaz et al. Pediatr Nephrol. 2023 Mar.

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.

Keywords: Children; HSP70; Heat shock proteins; UTI; Urinary tract infection.

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