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    Renal bcl-2/bax expression in childhood Henoch-Schonlein nephritis: prognostic importance?
    (Tubitak Scientific & Technological Research Council Turkey, 2013) Bek, Kenan; Oksal, Aysegul; Demircin, Gulay; Bulbul, Mehmet; Aydog, Ozlem; Delibas, Ali; Oner, Ayse
    Aim: To investigate the renal expression of apoptosis regulatory proteins b-cell lymphoma 2 (bcl-2) and bcl-2 associated X (bax) in children with Henoch-Schonlein nephritis (HSN) Materials and methods: Renal expression of antiapoptotic bcl-2 and proapoptotic bax proteins were studied immunohistochemically in 22 children with HSN. The kidneys of 5 children who died due to nonrenal reasons were used as the control. The patients were compared according to their renal histopathology and prognosis. Results: Nephrotic or nephrotic-nephritic renal involvement was the most common presentation. Histopathological findings were Class I in 1, Class II in 5, Class III in 10, Class IV in 4, and Class V in 2 patients. IgA staining was shown in all biopsies. Bcl-2 and bax proteins mainly showed tubular and crescentic expression. This was significantly different for bcl-2 in tubules and bax in distal tubules compared to the controls (P < 0.05). No significant difference between bax and bcl-2 expression was observed among patients. However the mean values of the bcl-2/bax ratio, that is, the balance between survival and apoptosis, were significantly higher in crescents of the severe histopathologic group and in distal tubules of the poor prognosis group (P < 0.05). Conclusion: A higher bcl-2/bax ratio, that is relative to the predominance of cell survival in distal tubules and crescents in HSN, seems to be a poor prognostic factor in children.
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    URINARY HSP70 IMPROVES DIAGNOSTIC ACCURACY FOR URINARY TRACT INFECTION IN CHILDREN: UTILISE STUDY
    (Springer, 2022) Yilmaz, Alev; Afonso, Alberto Caldas; Akil, Ipek; Aksu, Bagdagul; Alpay, Harika; Atmis, Bahriye; Aydog, Ozlem
    [Abstract Not Available]
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    Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study
    (Springer, 2023) Yilmaz, Alev; Afonso, Alberto Caldas; Akil, Ipek; Aksu, Bagdagul; Alpay, Harika; Atmis, Bahriye; Aydog, Ozlem
    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.
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    Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study
    (Springer, 2024) Aksu, Bagdagul; Afonso, Alberto Caldas; Akil, Ipek; Alpay, Harika; Atmis, Bahriye; Aydog, Ozlem; Bayazit, Aysun Karabay
    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.