Browsing by Author "Azukaitis 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