Browsing by Author "Bulut I.K."

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    Effects of nutritional Vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease
    (Oxford University Press, 2018) Lerch C.; Shroff R.; Wan M.; Rees L.; Aitkenhead H.; Bulut I.K.; Thurn D.; Bayazit A.K.; Niemirska A.; Canpolat N.; Duzova A.; Azukaitis K.; Yilmaz E.; Yalcinkaya F.; Harambat J.; Kiyak A.; Alpay H.; Habbig S.; Zaloszyc A.; Soylemezoglu O.; Candan C.; Rosales A.; Melk A.; Querfeld U.; Leifheit-Nestler M.; Sander A.; Schaefer F.; Haffner D.; Cortina G.; Arbeiter K.; Dusek J.; Ranchin B.; Fischbach M.; Zalosczyk A.; Galiano M.; Büscher R.; Gimpel C.; Kemper M.; Doyon A.; Wühl E.; Pohl M.; Wygoda S.; Jeck N.; Kranz B.; Wigger M.; Montini G.; Lugani F.; Testa S.; Vidal E.; Matteucci C.; Picca S.; Jankauskiene A.; Zurowska A.; Drodz D.; Tkaczyk M.; Urasinski T.; Litwin M.; Szczepanska M.; Texeira A.; Peco-Antic A.; Bucher B.; Laube G.; Anarat A.; Basin E.; Cakar N.; Bilginer Y.; Erdogan H.; Donmez O.; Balat A.; Caliskan S.; Civilibal M.; Emre S.; Ozcelik G.; Mir S.; Sözeri B.; Yavascan O.; Tabel Y.; Ertan P.; Prytula A.; Bachetta J.; Klaus G.; Geßner M.; Schmitt C.P.; Stabouli S.; Reusz G.; Verrina E.; Groothoff J.; Tondel C.; Gamero M.A.; Petrosyan E.; Bakkaloglu S.A.; Dursun I.
    Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23(FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). Methods: In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73 m2], and 40 with advanced CKD from the observational Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study (eGFR 24 mL/min/1.73 m2). In each study, vitamin D supplementation was started in 20 children and 20 matched children not receiving vitamin D served as controls. Measures were taken at baseline and after a median period of 8 months. Age- and gender-related standard deviation scores (SDSs) were calculated. Results: Before vitamin D supplementation, children in the ERGO study had normal FGF23 (median 0.31 SDS) and BAP (-0.10 SDS) but decreased Klotho and sclerostin (-0.77 and - 1.04 SDS, respectively), whereas 4C patients had increased FGF23 (3.87 SDS), BAP (0.78 SDS) and sclerostin (0.76 SDS) but normal Klotho (-0.27 SDS) levels. Vitamin D supplementation further increased FGF23 in 4C but not in ERGO patients. Serum Klotho and sclerostin normalized with vitamin D supplementation in ERGO but remained unchanged in 4C patients. BAP levels were unchanged in all patients. In the total cohort, significant effects of vitamin D supplementation were noted for Klotho at eGFR 40-70mL/min/1.73m2. Conclusions: Vitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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    Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease
    (Springer Verlag, 2019) Holle J.; Querfeld U.; Kirchner M.; Anninos A.; Okun J.; Thurn-Valsassina D.; Bayazit A.; Niemirska A.; Canpolat N.; Bulut I.K.; Duzova A.; Anarat A.; Shroff R.; Bilginer Y.; Caliskan S.; Candan C.; Harambat J.; Özcakar Z.B.; Soylemezoglu O.; Tschumi S.; Habbig S.; Yilmaz E.; Balat A.; Zurowska A.; Cakar N.; Kranz B.; Ertan P.; Melk A.; Azukaitis K.; Schaefer F.
    Background: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. Methods: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6–17 years with initial eGFR of 10–60 ml/min per 1.73 m2. Results: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 μmol/l (8.7) and 17.0 μmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. Conclusions: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort. © 2019, IPNA.
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    Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children
    (Elsevier B.V., 2019) Azukaitis K.; Ju W.; Kirchner M.; Nair V.; Smith M.; Fang Z.; Thurn-Valsassina D.; Bayazit A.; Niemirska A.; Canpolat N.; Bulut I.K.; Yalcinkaya F.; Paripovic D.; Harambat J.; Cakar N.; Alpay H.; Lugani F.; Mencarelli F.; Civilibal M.; Erdogan H.; Gellermann J.; Vidal E.; Tabel Y.; Gimpel C.; Ertan P.; Yavascan O.; Melk A.; Querfeld U.; Wühl E.; Kretzler M.; Schaefer F.; Arbeiter K.; Rosales A.; Dusek J.; Zaloszyc A.; Liebau M.; Weber L.; Muschiol E.; Büscher R.; Oh J.; Thurn-Valassina D.; Haffner D.; John U.; Wygoda S.; Jeck N.; Wigger M.; Testa S.; Murer L.; Matteucci C.; Jankauskiene A.; Drozdz D.; Zurowska A.; Zaniew M.; Litwin M.; Nimierska A.; Teixeira A.; Peco-Antic A.; Laube G.; Anarat A.; Duzova A.; Bilginer Y.; Caliskan S.; Mir S.; Sözeri B.; Kranz B.; Dorn B.; Baskin E.; Soylemezoglu O.; Emre S.; Candan C.; Kiyak A.; Ozcelik G.; Shroff R.; Rachin B.; Szczepanska M.; Donmez O.; Balat A.; Aksu N.; Yilmaz E.; Bakkaloglu A.; Ozaltin F.; Sallay P.; Bonzel K.-E.; Wingen A.-M.; Balasz I.; Trivelli A.; Perfumo F.; Müller-Wiefel D.-E.; Möller K.; Offner G.; Enke B.; Hadtstein C.; Mehls O.; Hohbach-Hohenfellner K.; Jeck N.; Klaus G.; Ardissino G.; Montini G.; Charbit M.; Niaudet P.; Afonso A.C.; Fernandes-Teixeira A.; Picca S.; Berg U.B.; Celsi G.; Fischbach M.; Terzic J.; Fydryk J.; Urasinski T.; Coppo R.; Peruzzi L.; Grenda R.; Neuhaus T.J.
    Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6–17 years with baseline estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69–0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD. © 2019 International Society of Nephrology
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    Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study
    (Springer Science and Business Media Deutschland GmbH, 2023) Yilmaz A.; Afonso A.C.; Akil I.; Aksu B.; 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.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Nayir A.; Obrycki L.; Omer B.; Ozdemir E.M.; Ozkayin N.; Paripovic D.; Pehlivanoglu C.; Saygili S.; Schaefer S.; Sonmez F.; Tabel Y.; Tas N.; Tasdemir M.; Teixeira A.; Tekcan D.; Tulpar S.; Turkkan O.N.; Uysal B.; Uysalol M.; Vaiciuniene D.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Schaefer F.; Topaloglu R.
    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. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to International Pediatric Nephrology Association.
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    The relationship between urine heat shock protein 70 and congenital anomalies of the kidney and urinary tract: UTILISE study
    (Frontiers Media SA, 2023) Aksu B.; Afonso A.C.; Akil I.; Alpay H.; Atmis B.; Aydog O.; Bakkaloglu S.; Bayazıt A.K.; Bayram M.T.; Bilge I.; Bulut I.K.; Cetinkaya A.P.G.; Comak E.; Demir B.K.; Dincel N.; Donmez O.; Durmus M.A.; Dursun H.; Dusunsel R.; Duzova A.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Obrycki L.; Omer B.; Misirli Ozdemir E.; 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 O.N.; Uysal B.; Uysalol M.; Vitkevic R.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Yilmaz A.
    Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are defined as structural malformations of the kidney and/or urinary tract. Heat shock proteins (HSPs) are expressed in the kidney in response to cellular changes, such as thermal, hemodynamic, osmotic, inflammatory, and mechanical stresses. This study aimed to assess uHSP70 levels during acute urinary tract infections (UTI) and non-infection periods in patients with CAKUT, and to evaluate whether uHSP70 is elevated in CAKUT subtypes. Methods: Among patients with CAKUT, 89 patients with UTI (CAKUT-A), 111 without UTI (CAKUT-B), and 74 healthy children were included in the study. uHSP70 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: uHSP70 level was significantly higher in the CAKUT-A group than in the CAKUT-B and healthy control groups (p < 0.0001). Moreover, the level of uHSP70 was significantly higher in the CAKUT-B group than in the control group (p < 0.0001), but was not different between the CAKUT subtypes (p > 0.05). Conclusion: Urine HSP70 can also be used to predict UTI in patients with CAKUT. Moreover, uHSP70 levels were higher in children with CAKUT during the non-infectious period than in healthy controls. This suggests that children with CAKUT are at risk of chronic non-infectious damage. Copyright © 2024 Aksu, Afonso, Akil, Alpay, Atmis, Aydog, Bakkaloglu, Bayazıt, Bayram, Bilge, Bulut, Cetinkaya, Comak, Demir, Dincel, Donmez, Durmus, Dursun, Dusunsel, Duzova, Ertan, Gedikbasi, Goknar, Guven, Hacihamdioglu, Jankauskiene, Kalyoncu, Kavukcu, Kenan, Kucuk, Kural, Litwin, Montini, Morello, Obrycki, Omer, Misirli Ozdemir, Ozkayin, Paripovic, Pehlivanoglu, Saygili, Schaefer, Schaefer, Sonmez, Tabel, Tas, Tasdemir, Teixeira, Tekcan, Topaloglu, Tulpar, Turkkan, Uysal, Uysalol, Vitkevic, Yavuz, Yel, Yildirim, Yildirim, Yildiz, Yuksel, Yurtseven and Yilmaz.
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    Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study
    (Springer Science and Business Media Deutschland GmbH, 2024) 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.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Obrycki L.; Omer B.; Oner H.A.; Ozdemir E.M.; 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 O.N.; Uysal B.; Uysalol M.; Vitkevic R.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Yilmaz A.
    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.]. © 2023, The Author(s), under exclusive licence to International Pediatric Nephrology Association.