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. 2024 Feb;39(2):483-491.
doi: 10.1007/s00467-023-06063-0. Epub 2023 Jul 18.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study

Bagdagul Aksu  1   2 , Alberto Caldas Afonso  3 , Ipek Akil  4 , Harika Alpay  5 , Bahriye Atmis  6   7 , Ozlem Aydog  8 , Aysun Karabay Bayazıt  7 , Meral Torun Bayram  9 , Ilmay Bilge  10 , Ipek Kaplan Bulut  11 , Bahar Buyukkaragoz  12 , Elif Comak  13 , Belde Kasap Demir  14   15 , Nida Dincel  16 , Osman Donmez  17 , Mehmet Akif Durmus  18 , Hasan Dursun  19 , Ruhan Dusunsel  20 , Ali Duzova  21 , Pelin Ertan  4 , Asuman Gedikbasi  22 , Nilufer Goknar  23 , Sercin Guven  5 , Duygu Hacihamdioglu  24 , Augustina Jankauskiene  25 , Mukaddes Kalyoncu  26 , Salih Kavukcu  9 , Bahriye Uzun Kenan  12 , Nuran Kucuk  27 , Bahar Kural  28 , Mieczysław Litwin  29 , Giovanni Montini  30   31 , William Morello  30 , Lukasz Obrycki  29 , Beyhan Omer  32 , Huseyin Adil Oner  33 , Ebru Misirli Ozdemir  34 , Nese Ozkayin  35 , Dusan Paripovic  36 , Cemile Pehlivanoglu  37 , Seha Saygili  38 , Franz Schaefer  39 , Susanne Schaefer  39 , Ferah Sonmez  40 , Yilmaz Tabel  41 , Nesrin Tas  21 , Mehmet Tasdemir  10   42 , Ana Teixeira  3 , Demet Tekcan  8 , Rezan Topaloglu  21 , Sebahat Tulpar  43 , Ozde Nisa Turkkan  5 , Berfin Uysal  44   45 , Metin Uysalol  46 , Renata Vitkevic  25 , Sevgi Yavuz  47 , Sibel Yel  20 , Tarik Yildirim  48 , Zeynep Yuruk Yildirim  49   33 , Nurdan Yildiz  5 , Selcuk Yuksel  50 , Eray Yurtseven  51 , Alev Yilmaz  49   33
Affiliations

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study

Bagdagul Aksu et al. Pediatr Nephrol. 2024 Feb.

Abstract

Background: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study.

Methods: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI.

Results: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001).

Conclusions: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: TLR4; Toll-like receptor 4; UTI; UTILISE study; Urinary tract infection.

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References

    1. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management (2011) Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 128:595–610 - DOI
    1. Subcommittee on Urinary Tract Infection (2016) Reaffirmation of AAP clinical practice guideline: the diagnosis and management of the initial urinary tract infection in febrile infants and young children 2–24 months of age. Pediatrics 138:E20163026 - DOI
    1. Saha D, Patel J, Buckingham D, Thornton D, Barber T, Watson JR (2017) Urine culture follow-up and antimicrobial stewardship in a pediatric urgent care network. Pediatrics 139:e20162103 - DOI - PubMed
    1. Mayeux R (2004) Biomarkers: potential uses and limitations. NeuroRx 1:182–188 - DOI - PubMed - PMC
    1. Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Ann Rev Immunol 21:335–376 - DOI

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