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

Bagdagul Aksu; Alberto Caldas Afonso; Ipek Akil; 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; Lukasz Obrycki; Beyhan Omer; Huseyin Adil Oner; Ebru Misirli Ozdemir; Nese Ozkayin; Dusan Paripovic; Cemile Pehlivanoglu; Seha Saygili; Franz Schaefer; Susanne Schaefer; Ferah Sonmez; Yilmaz Tabel; Nesrin Tas; Mehmet Tasdemir; Ana Teixeira; Demet Tekcan; Rezan Topaloglu; Sebahat Tulpar; Ozde Nisa Turkkan; Berfin Uysal; Metin Uysalol; Renata Vitkevic; Sevgi Yavuz; Sibel Yel; Tarik Yildirim; Zeynep Yuruk Yildirim; Nurdan Yildiz; Selcuk Yuksel; Eray Yurtseven; Alev Yilmaz

doi:10.1007/s00467-023-06063-0

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

Bagdagul Aksu, Alberto Caldas Afonso, Ipek Akil, 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 ErtanAsuman 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, Lukasz Obrycki, Beyhan Omer, Huseyin Adil Oner, Ebru Misirli Ozdemir, Nese Ozkayin, Dusan Paripovic, Cemile Pehlivanoglu, Seha Saygili, Franz Schaefer, Susanne Schaefer, Ferah Sonmez, Yilmaz Tabel, Nesrin Tas, Mehmet Tasdemir, Ana Teixeira, Demet Tekcan, Rezan Topaloglu, Sebahat Tulpar, Ozde Nisa Turkkan, Berfin Uysal, Metin Uysalol, Renata Vitkevic, Sevgi Yavuz, Sibel Yel, Tarik Yildirim, Zeynep Yuruk Yildirim, Nurdan Yildiz, Selcuk Yuksel, Eray Yurtseven, Alev Yilmaz

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1 Citation (Scopus)

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. Graphical abstract: [Figure not available: see fulltext.].

Original language	English
Pages (from-to)	483-491
Number of pages	9
Journal	Pediatric Nephrology
Volume	39
Issue number	2
DOIs	https://doi.org/10.1007/s00467-023-06063-0
Publication status	Published - Feb 2024
Externally published	Yes

Keywords

TLR4
Toll-like receptor 4
UTI
UTILISE study
Urinary tract infection

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10.1007/s00467-023-06063-0

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Aksu, B., Afonso, A. C., Akil, I., Alpay, H., Atmis, B., Aydog, O., Bayazıt, A. K., Bayram, M. T., Bilge, I., Bulut, I. K., Buyukkaragoz, B., Comak, E., Demir, B. K., Dincel, N., Donmez, O., Durmus, M. A., Dursun, H., Dusunsel, R., Duzova, A., ... Yilmaz, A. (2024). Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study. Pediatric Nephrology, 39(2), 483-491. https://doi.org/10.1007/s00467-023-06063-0

@article{aa087b091dd045cc94380fcdbbb5f277,

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

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. Graphical abstract: [Figure not available: see fulltext.].",

keywords = "TLR4, Toll-like receptor 4, UTI, UTILISE study, Urinary tract infection",

author = "Bagdagul Aksu and Afonso, {Alberto Caldas} and Ipek Akil and Harika Alpay and Bahriye Atmis and Ozlem Aydog and Bayazıt, {Aysun Karabay} and Bayram, {Meral Torun} and Ilmay Bilge and Bulut, {Ipek Kaplan} and Bahar Buyukkaragoz and Elif Comak and Demir, {Belde Kasap} and Nida Dincel and Osman Donmez and Durmus, {Mehmet Akif} and Hasan Dursun and Ruhan Dusunsel and Ali Duzova and Pelin Ertan and Asuman Gedikbasi and Nilufer Goknar and Sercin Guven and Duygu Hacihamdioglu and Augustina Jankauskiene and Mukaddes Kalyoncu and Salih Kavukcu and Kenan, {Bahriye Uzun} and Nuran Kucuk and Bahar Kural and Mieczys{\l}aw Litwin and Giovanni Montini and William Morello and Lukasz Obrycki and Beyhan Omer and Oner, {Huseyin Adil} and Ozdemir, {Ebru Misirli} and Nese Ozkayin and Dusan Paripovic and Cemile Pehlivanoglu and Seha Saygili and Franz Schaefer and Susanne Schaefer and Ferah Sonmez and Yilmaz Tabel and Nesrin Tas and Mehmet Tasdemir and Ana Teixeira and Demet Tekcan and Rezan Topaloglu and Sebahat Tulpar and Turkkan, {Ozde Nisa} and Berfin Uysal and Metin Uysalol and Renata Vitkevic and Sevgi Yavuz and Sibel Yel and Tarik Yildirim and Yildirim, {Zeynep Yuruk} and Nurdan Yildiz and Selcuk Yuksel and Eray Yurtseven and Alev Yilmaz",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to International Pediatric Nephrology Association.",

year = "2024",

month = feb,

doi = "10.1007/s00467-023-06063-0",

language = "English",

volume = "39",

pages = "483--491",

journal = "Pediatric Nephrology",

issn = "0931-041X",

publisher = "Springer Verlag",

number = "2",

}

Aksu, B, Afonso, AC, Akil, I, Alpay, H, Atmis, B, Aydog, O, Bayazıt, AK, Bayram, MT, Bilge, I, Bulut, IK, Buyukkaragoz, B, Comak, E, Demir, BK, Dincel, N, Donmez, O, Durmus, MA, Dursun, H, Dusunsel, R, Duzova, A, Ertan, P, Gedikbasi, A, Goknar, N, Guven, S, Hacihamdioglu, D, Jankauskiene, A, Kalyoncu, M, Kavukcu, S, Kenan, BU, Kucuk, N, Kural, B, Litwin, M, Montini, G, Morello, W, Obrycki, L, Omer, B, Oner, HA, Ozdemir, EM, Ozkayin, N, Paripovic, D, Pehlivanoglu, C, Saygili, S, Schaefer, F, Schaefer, S, Sonmez, F, Tabel, Y, Tas, N, Tasdemir, M, Teixeira, A, Tekcan, D, Topaloglu, R, Tulpar, S, Turkkan, ON, Uysal, B, Uysalol, M, Vitkevic, R, Yavuz, S, Yel, S, Yildirim, T, Yildirim, ZY, Yildiz, N, Yuksel, S, Yurtseven, E & Yilmaz, A 2024, 'Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study', Pediatric Nephrology, vol. 39, no. 2, pp. 483-491. https://doi.org/10.1007/s00467-023-06063-0

TY - JOUR

T1 - Urine soluble TLR4 levels may contribute to predict urinary tract infection in children

T2 - the UTILISE Study

AU - Aksu, Bagdagul

AU - Afonso, Alberto Caldas

AU - Akil, Ipek

AU - Alpay, Harika

AU - Atmis, Bahriye

AU - Aydog, Ozlem

AU - Bayazıt, Aysun Karabay

AU - Bayram, Meral Torun

AU - Bilge, Ilmay

AU - Bulut, Ipek Kaplan

AU - Buyukkaragoz, Bahar

AU - Comak, Elif

AU - Demir, Belde Kasap

AU - Dincel, Nida

AU - Donmez, Osman

AU - Durmus, Mehmet Akif

AU - Dursun, Hasan

AU - Dusunsel, Ruhan

AU - Duzova, Ali

AU - Ertan, Pelin

AU - Gedikbasi, Asuman

AU - Goknar, Nilufer

AU - Guven, Sercin

AU - Hacihamdioglu, Duygu

AU - Jankauskiene, Augustina

AU - Kalyoncu, Mukaddes

AU - Kavukcu, Salih

AU - Kenan, Bahriye Uzun

AU - Kucuk, Nuran

AU - Kural, Bahar

AU - Litwin, Mieczysław

AU - Montini, Giovanni

AU - Morello, William

AU - Obrycki, Lukasz

AU - Omer, Beyhan

AU - Oner, Huseyin Adil

AU - Ozdemir, Ebru Misirli

AU - Ozkayin, Nese

AU - Paripovic, Dusan

AU - Pehlivanoglu, Cemile

AU - Saygili, Seha

AU - Schaefer, Franz

AU - Schaefer, Susanne

AU - Sonmez, Ferah

AU - Tabel, Yilmaz

AU - Tas, Nesrin

AU - Tasdemir, Mehmet

AU - Teixeira, Ana

AU - Tekcan, Demet

AU - Topaloglu, Rezan

AU - Tulpar, Sebahat

AU - Turkkan, Ozde Nisa

AU - Uysal, Berfin

AU - Uysalol, Metin

AU - Vitkevic, Renata

AU - Yavuz, Sevgi

AU - Yel, Sibel

AU - Yildirim, Tarik

AU - Yildirim, Zeynep Yuruk

AU - Yildiz, Nurdan

AU - Yuksel, Selcuk

AU - Yurtseven, Eray

AU - Yilmaz, Alev

PY - 2024/2

Y1 - 2024/2

N2 - 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. Graphical abstract: [Figure not available: see fulltext.].

AB - 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. Graphical abstract: [Figure not available: see fulltext.].

KW - TLR4

KW - Toll-like receptor 4

KW - UTI

KW - UTILISE study

KW - Urinary tract infection

UR - http://www.scopus.com/inward/record.url?scp=85165011036&partnerID=8YFLogxK

U2 - 10.1007/s00467-023-06063-0

DO - 10.1007/s00467-023-06063-0

M3 - Article

C2 - 37462743

AN - SCOPUS:85165011036

SN - 0931-041X

VL - 39

SP - 483

EP - 491

JO - Pediatric Nephrology

JF - Pediatric Nephrology

IS - 2

ER -

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

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