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Öğe Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease(Oxford Univ Press, 2018) Lerch, Christian; Shroff, Rukshana; Wan, Mandy; Rees, Lesley; Aitkenhead, Helen; Bulut, Ipek Kaplan; Thurn, Daniela; Bayazit, Aysun Karabay; Niemirska, Anna; Canpolat, Nur; Duzova, Ali; Azukaitis, Karolis; Yilmaz, Ebru; Yalcinkaya, Fatos; Harambat, Jerome; Kiyak, Aysel; Alpay, Harika; Habbig, Sandra; Zaloszyc, Ariane; Soylemezoglu, Oguz; Candan, Cengiz; Rosales, Alejandra; Melk, Anette; Querfeld, Uwe; Leifheit-Nestler, Maren; Sander, Anja; Schaefer, Franz; Haffner, Dieter; Cortina, G.; Arbeiter, K.; Dusek, J.; Harambat, J.; Ranchin, B.; Fischbach, M.; Zalosczyk, A.; Querfeld, U.; Habbig, S.; Galiano, M.; Buescher, R.; Gimpel, C.; Kemper, M.; Melk, A.; Thurn, D.; Schaefer, F.; Doyon, A.; Wuehl, 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.; Azukaitis, K.; Zurowska, A.; Drodz, D.; Tkaczyk, M.; Urasinski, T.; Litwin, M.; Niemirska, A.; Szczepanska, M.; Texeira, A.; Peco-Antic, A.; Bucher, B.; Laube, G.; Anarat, A.; Bayazit, A. K.; Yalcinkaya, F.; Basin, E.; Cakar, N.; Soylemezoglu, O.; Duzova, A.; Bilginer, Y.; Erdogan, H.; Donmez, O.; Balat, A.; Kiyak, A.; Caliskan, S.; Canpolat, N.; Candan, C.; Civilibal, M.; Emre, S.; Alpay, H.; Ozcelik, G.; Mir, S.; Sozeri, B.; Yavascan, O.; Tabel, Y.; Ertan, P.; Yilmaz, E.; Shroff, R.; Prytula, A.; Bachetta, J.; Haffner, D.; 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.; Shroff, R.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 m(2)], 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 40-70 mL/min/1.73 m(2). Conclusions. Vitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD.Öğe Impact of recombinant growth hormone (rGH) therapy on bone metabolism in children with chronic kidney disease (CKD): Findings from the 4C Study(Springer, 2013) Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun K.; Canpolat, Nur; Sozeri, Betul; Bacchetta, Justine; Gondan, Matthias; Haffner, Dieter; Querfeld, Uwe; Schaefer, FranzÖğe Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children(Elsevier Science Inc, 2019) Azukaitis, Karolis; Ju, Wenjun; Kirchner, Marietta; Nair, Viji; Smith, Michelle; Fang, Zhiyin; Thurn-Valsassina, Daniela; Bayazit, Aysun; Niemirska, Anna; Canpolat, Nur; Bulut, Ipek Kaplan; Yalcinkaya, Fatos; Paripovic, Dusan; Harambat, Jerome; Cakar, Nilgun; Alpay, Harika; Lugani, Francesca; Mencarelli, Francesca; Civilibal, Mahmut; Erdogan, Hakan; Gellermann, Jutta; Vidal, Enrico; Tabel, Yilmaz; Gimpel, Charlotte; Ertan, Pelin; Yavascan, Onder; Melk, Anette; Querfeld, Uwe; Wuehl, Elke; Kretzler, Matthias; Schaefer, Franz; Arbeiter, Klaus; Rosales, Alejandra; Dusek, Jiri; Zaloszyc, Ariane; Querfeld, Uwe; Gellermann, Jutta; Liebau, Max; Weber, Lutz; Muschiol, Evelin; Buescher, Rainer; Oh, Jun; Melk, Anette; Thurn-Valassina, Daniela; Haffner, Dieter; Schaefer, Franz; Gimpel, Charlotte; John, Ulrike; Wygoda, Simone; Jeck, Nikola; Wigger, Marianne; Testa, Sara; Murer, Luisa; Matteucci, Chiara; Jankauskiene, Augustina; Azukaitis, Karolis; Drozdz, Dorota; Lugani, Francesca; Zurowska, Aleksandra; Zaniew, Marcin; Litwin, Mieczyslaw; Nimierska, Anna; Teixeira, Ana; Peco-Antic, Amira; Paripovic, Dusan; Laube, Guido; Dali, Cocuk Nefrolojisi Bilim; Anarat, Ali; Bayazit, Aysun; Duzova, Ali; Bilginer, Yelda; Caliskan, Salim; Canpolat, Nur; Civilibal, Mahmut; Mir, Sevgi; Soezeri, Betul; Kranz, Brigitta; Mencarelli, Francesca; Dorn, Brigitte; Yalcinkaya, Fatos; Baskin, Esra; Cakar, Nilgun; Soylemezoglu, Oguz; Emre, Sevinc; Candan, Cengiz; Kiyak, Aysel; Ozcelik, Gul; Alpay, Harika; Shroff, Rukshana; Rachin, Bruno; Harambat, Jerome; Szczepanska, Maria; Erdogan, Hakan; Donmez, Osman; Balat, Ayse; Aksu, Nejat; Tabel, Yilmaz; Ertan, Pelin; Yilmaz, Ebru; Anarat, Ali; Bakkaloglu, Aysin; Ozaltin, Fatih; Peco-Antic, Amira; Querfeld, Uwe; Gellermann, Jutta; Sallay, Peter; Drozdz, Dorota; Bonzel, Klaus-Eugen; Wingen, Anna-Margrete; Urowska, Aleksandra Z.; Balasz, Irena; Trivelli, Antonella; Perfumo, Francesco; Mueller-Wiefel, Dirk-Erhard; Moeller, Kerstin; Offner, Gisela; Enke, Barbara; Wuehl, Elke; Hadtstein, Charlotte; Mehls, Otto; Schaefer, Franz; Emre, Sevinc; Caliskan, Salim; Mir, Sevgi; Wygoda, Simone; Hohbach-Hohenfellner, Katharina; Jeck, Nickola; Klaus, Guenter; Ardissino, Gianluigi; Testa, Sara; Montini, Giovanni; Charbit, Marina; Niaudet, Patrick; Afonso, Alberto Caldas; Fernandes-Teixeira, Ana; Dusek, Jiri; Matteucci, Chiara; Picca, Stefano; Wigger, Marianne; Berg, Ulla B.; Celsi, Giovanni; Fischbach, Michel; Terzic, Joelle; Fydryk, Janusz; Urasinski, Tomasz; Coppo, Rosanna; Peruzzi, Licia; Arbeiter, Klaus; Jankauskiene, Augustina; Grenda, Ryszard; Litwin, Mieczyslaw; Neuhaus, Thomas 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 m(2). 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 m(2), and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m(2), 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.Öğe Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease(Public Library Science, 2015) Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sozeri, Betul; Bacchetta, Justine; Balat, Ayse; Buesher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Guenter; Mir, Sevgi; Ozcelik, Gul; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wuehl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, FranzObjectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73m(2). 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.Öğe Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease(Mosby-Elsevier, 2018) Burgmaier, Kathrin; Kunzmann, Kevin; Ariceta, Gema; Bergmann, Carsten; Buescher, Anja Katrin; Burgmaier, Mathias; Dursun, Ismail; Duzova, Ali; Eid, Loai; Erger, Florian; Feldkoetter, Markus; Galiano, Matthias; Gessner, Michaela; Goebel, Heike; Gokce, Ibrahim; Haffner, Dieter; Hooman, Nakysa; Hoppe, Bernd; Jankauskiene, Augustina; Klaus, Guenter; Koenig, Jens; Litwin, Mieczyslaw; Massella, Laura; Mekahli, Djalila; Melek, Engin; Mir, Sevgi; Pape, Lars; Prikhodina, Larisa; Ranchin, Bruno; Schild, Raphael; Seeman, Tomas; Sever, Late; Shroff, Rukshana; Soliman, Neveen A.; Stabouli, Stella; Stanczyk, Malgorzata; Tabel, Yilmaz; Taranta-Janusz, Katarzyna; Testa, Sara; Thumfart, Julia; Topaloglu, Rezan; Weber, Lutz Thorsten; Wicher, Dorota; Wuehl, Elke; Wygoda, Simone; Yilmaz, Alev; Zachwieja, Katarzyna; Zagozdzon, Ilona; Zerres, Klaus; Doetsch, Joerg; Schaefer, Franz; Liebau, Max ChristophObjective To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. Study design A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. Results Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. Conclusions This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life. may be helpful in prenatal parental counseling in cases of suspected ARPKD.Öğe TREATMENT WITH ACTIVE VITAMIN D DOES NOT IMPROVE LEFT VENTRICULAR HYPERTROPHY BUT FURTHER INCREASES FGF23 AND ACCELERATES CKD PROGRESSION IN CHILDREN(Oxford Univ Press, 2020) Leifheit-Nestler, Maren; Schoen, Anne; Deppe, Jennifer; Bayazit, Aysun Karabay; Obrycki, Lukasz; Canpolat, Nur; Haffner, Dieter[No abstract available]