Urinary HSP70 improves diagnostic accuracy for urinary tract infection

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.

C1 [Yilmaz, Alev; Aksu, Bagdagul; Nayir, Ahmet; Turkkan, Ozde Nisa; Yildirim, Zeynep Yuruk] Istanbul Univ, Istanbul Fac Med, Div Pediat Nephrol, Istanbul, Turkey.

[Yilmaz, Alev; Aksu, Bagdagul; Nayir, Ahmet; Yildirim, Zeynep Yuruk] Istanbul Univ, Inst Child Hlth, Dept Pediat Basic Sci, Istanbul, Turkey.

[Afonso, Alberto Caldas; Teixeira, Ana] Ctr Hosp Univ Porto, Ctr Materno Infantil Norte, Div Pediat Nephrol, Porto, Portugal.

[Akil, Ipek; Ertan, Pelin] Celal Bayar Univ, Fac Med, Div Pediat Nephrol, Manisa, Turkey.

[Alpay, Harika; Guven, Sercin; Yildiz, Nurdan] Marmara Univ, Fac Med, Div Pediat Nephrol, Istanbul, Turkey.

[Atmis, Bahriye] Erzurum Training & Res Hosp, Pediat Nephrol, Erzurum, Turkey.

[Atmis, Bahriye; Bayazit, Aysun Karabay] Cukurova Univ, Fac Med, Div Pediat Nephrol, Adana, Turkey.

[Aydog, Ozlem; Tekcan, Demet] Ondokuz Mayis Univ, Fac Med, Div Pediat Nephrol, Samsun, Turkey.

[Bayram, Meral Torun; Kavukcu, Salih] Dokuz Eylul Univ, Fac Med, Div Pediat Nephrol, Izmir, Turkey.

[Bilge, Ilmay; Tasdemir, Mehmet] Koc Univ, Sch Med, Dept Pediat, Div Pediat Nephrol, Istanbul, Turkey.

[Bulut, Ipek Kaplan] Ege Univ, Fac Med, Div Pediat Nephrol, Izmir, Turkey.

[Buyukkaragoz, Bahar; Kenan, Bahriye Uzun] Gazi Univ, Fac Med, Div Pediat Nephrol, Ankara, Turkey.

[Comak, Elif] Akdeniz Univ, Fac Med, Div Pediat Nephrol, Antalya, Turkey.

[Demir, Belde Kasap] Univ Hlth Sci, Tepecik Training & Res Hosp, Div Pediat Nephrol, Izmir, Turkey.

[Demir, Belde Kasap] Izmir Katip Celebi Univ, Div Pediat Nephrol, Fac Med, Izmir, Turkey.

[Dincel, Nida] Univ Hlth Sci, Dr Behcet Uz Children Dis Training & Res Hosp, Div Pediat Nephrol, Izmir, Turkey.

[Donmez, Osman] Uludag Univ, Fac Med, Div Pediat Nephrol, Bursa, Turkey.

[Durmus, Mehmet Akif] Istanbul Univ, Istanbul Fac Med, Dept Med Microbiol, Istanbul, Turkey.

[Dursun, Hasan] Univ Hlth Sci, Okmeydani Training & Res Hosp, Div Pediat Nephrol, Istanbul, Turkey.

[Dusunsel, Ruhan; Yel, Sibel] Erciyes Univ, Fac Med, Div Pediat Nephrol, Kayseri, Turkey.

[Duzova, Ali; Tas, Nesrin; Topaloglu, Rezan] Hacettepe Univ, Fac Med, Div Pediat Nephrol, Ankara, Turkey.

[Gedikbasi, Asuman] Istanbul Univ, Inst Child Hlth, Dept Rare Dis, Istanbul, Turkey.

[Goknar, Nilufer] Univ Hlth Sci, Bagcilar Training & Res Hosp, Div Pediat Nephrol, Istanbul, Turkey.

[Hacihamdioglu, Duygu] Bahcesehir Univ, Fac Med, Div Pediat Nephrol, Istanbul, Turkey.

[Jankauskiene, Augustina; Vaiciuniene, Daiva] Vilnius Univ, Inst Expt & Clin Med, Clin Pediat, Vilnius, Lithuania.

[Kalyoncu, Mukaddes] Karadeniz Tech Univ, Div Pediat Nephrol, Fac Med, Trabzon, Turkey.

[Kucuk, Nuran] Kartal Training & Res Hosp, Div Pediat Nephrol, Istanbul, Turkey.

[Kural, Bahar] Hlth Sci Univ, Bakirkoy Sadi Konuk Training & Res Hosp, Dept Pediat, Istanbul, Turkey.

[Obrycki, Lukasz; Litwin, Mieczyslaw] Childrens Mem Hlth Inst, Div Nephrol, Kidney Transplantat & Hypertens, Warsaw, Poland.

[Montini, Giovanni; Morello, William] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Pediat Nephrol Dialysis & Transplant Unit, Milan, Italy.

[Montini, Giovanni] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.

[Omer, Beyhan] Istanbul Univ, Istanbul Fac Med, Dept Biochem, Istanbul, Turkey.

[Ozdemir, Ebru Misirli] Okmeydani Training & Res Hosp, Dept Pediat, Istanbul, Turkey.

[Ozkayin, Nese] Trakya Univ, Fac Med, Div Pediat Nephrol, Edirne, Turkey.

[Paripovic, Dusan] Univ Childrens Hosp, Div Pediat Nephrol, Belgrade, Serbia.

[Pehlivanoglu, Cemile] Umraniye Training & Res Hosp, Div Pediat Nephrol, Istanbul, Turkey.

[Saygili, Seha] Istanbul Univ Cerrahpasa, Cerrahpasa Fac Med, Div Pediat Nephrol, Istanbul, Turkey.

[Schaefer, Susanne; Schaefer, Franz] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany.

[Sonmez, Ferah] Adnan Menderes Univ, Fac Med, Div Pediat Nephrol, Aydin, Turkey.

[Tabel, Yilmaz] Inonu Univ, Fac Med, Div Pediat Nephrol, Malatya, Turkey.

[Tulpar, Sebahat] Bakirkoy Dr Sadi Konuk Training & Res Hosp, Div Pediat Nephrol, Istanbul, Turkey.

[Uysal, Berfin] Dortcelik Childrens Hosp, Div Pediat Nephrol, Bursa, Turkey.

[Uysal, Berfin] Bursa City Hosp, Div Pediat Nephrol, Bursa, Turkey.

[Uysalol, Metin] Istanbul Univ, Istanbul Fac Med, Div Pediat Emergency, Istanbul, Turkey.

[Yavuz, Sevgi] Univ Hlth Sci, Kanuni Sultan Suleyman Res & Training Hosp, Dept Pediat, Div Pediat Nephrol, Istanbul, Turkey.

[Yildirim, Tarik] Univ Hlth Sci, Kanuni Sultan Suleyman Res & Training Hosp, Dept Pediat, Istanbul, Turkey.

[Yuksel, Selcuk] Pamukkale Univ, Fac Med, Div Pediat Nephrol, Denizli, Turkey.

[Yurtseven, Eray] Istanbul Univ, Istanbul Fac Med, Dept Biostat, Istanbul, Turkey.