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Original ArticlesChronic Kidney Disease
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Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD

Anke Doyon, Bettina Schmiedchen, Anja Sander, Aysun Bayazit, Ali Duzova, Nur Canpolat, Daniela Thurn, Karolis Azukaitis, Ali Anarat, Justine Bacchetta, Sevgi Mir, Rukshana Shroff, Ebru Yilmaz, Cengiz Candan, Markus Kemper, Michel Fischbach, Gerard Cortina, Günter Klaus, Matthias Wuttke, Anna Köttgen, Anette Melk, Uwe Querfeld and Franz Schaefer
CJASN July 2016, 11 (7) 1145-1153; DOI: https://doi.org/10.2215/CJN.10210915
Anke Doyon
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Bettina Schmiedchen
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Anja Sander
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Aysun Bayazit
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Ali Duzova
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Nur Canpolat
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Daniela Thurn
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Karolis Azukaitis
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Ali Anarat
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Justine Bacchetta
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Sevgi Mir
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Rukshana Shroff
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Ebru Yilmaz
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Cengiz Candan
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Markus Kemper
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Michel Fischbach
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Gerard Cortina
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Günter Klaus
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Matthias Wuttke
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Anna Köttgen
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Anette Melk
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Uwe Querfeld
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Franz Schaefer
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Abstract

Background and objectives Vitamin D deficiency is endemic in children with CKD. We sought to investigate the association of genetic disposition, environmental factors, vitamin D supplementation, and renal function on vitamin D status in children with CKD.

Design, setting, participants, & measurements Serum 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D, and 24,25-dihydroxy-vitamin D concentrations were measured cross-sectionally in 500 children from 12 European countries with CKD stages 3–5. All patients were participants of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study, had CKD stage 3–5, and were age 6–18 years old. Patients were genotyped for single-nucleotide polymorphisms in the genes encoding 25-hydroxylase, vitamin D binding protein, 7-dehydrocholesterol reductase, and 24-hydroxylase. Associations of genetic status, season, local solar radiation, oral vitamin D supplementation, and disease-associated factors with vitamin D status were assessed.

Results Two thirds of patients were vitamin D deficient (25-hydroxy-vitamin D <16 ng/ml). 25-Hydroxy-vitamin D concentrations varied with season and were twofold higher in vitamin D–supplemented patients (21.6 [14.1] versus 10.4 [10.1] ng/ml; P<0.001). Glomerulopathy, albuminuria, and girls were associated with lower 25-hydroxy-vitamin D levels. 24,25-dihydroxy-vitamin D levels were closely correlated with 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D (r=0.87 and r=0.55; both P<0.001). 24,25-dihydroxy-vitamin D concentrations were higher with higher c-terminal fibroblast growth factor 23 and inversely correlated with intact parathyroid hormone. Whereas 25-hydroxy-vitamin D levels were independent of renal function, 24,25-dihydroxy-vitamin D levels were lower with lower eGFR. Vitamin D deficiency was more prevalent in Turkey than in other European regions independent of supplementation status and disease-related factors. Single-nucleotide polymorphisms in the vitamin D binding protein gene were independently associated with lower 25-hydroxy-vitamin D and higher 24,25-dihydroxy-vitamin D.

Conclusions Disease-related factors and vitamin D supplementation are the main correlates of vitamin D status in children with CKD. Variants in the vitamin D binding protein showed weak associations with the vitamin D status.

  • Vitamin D
  • chronic kidney disease
  • vitamin D deficiency
  • vitamin d supplementation
  • albuminuria
  • Child
  • Humans
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic
  • 25-hydroxyvitamin D
  • Received September 23, 2015.
  • Accepted March 17, 2016.
  • Copyright © 2016 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 11 (7)
Clinical Journal of the American Society of Nephrology
Vol. 11, Issue 7
July 07, 2016
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Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD
Anke Doyon, Bettina Schmiedchen, Anja Sander, Aysun Bayazit, Ali Duzova, Nur Canpolat, Daniela Thurn, Karolis Azukaitis, Ali Anarat, Justine Bacchetta, Sevgi Mir, Rukshana Shroff, Ebru Yilmaz, Cengiz Candan, Markus Kemper, Michel Fischbach, Gerard Cortina, Günter Klaus, Matthias Wuttke, Anna Köttgen, Anette Melk, Uwe Querfeld, Franz Schaefer
CJASN Jul 2016, 11 (7) 1145-1153; DOI: 10.2215/CJN.10210915

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Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD
Anke Doyon, Bettina Schmiedchen, Anja Sander, Aysun Bayazit, Ali Duzova, Nur Canpolat, Daniela Thurn, Karolis Azukaitis, Ali Anarat, Justine Bacchetta, Sevgi Mir, Rukshana Shroff, Ebru Yilmaz, Cengiz Candan, Markus Kemper, Michel Fischbach, Gerard Cortina, Günter Klaus, Matthias Wuttke, Anna Köttgen, Anette Melk, Uwe Querfeld, Franz Schaefer
CJASN Jul 2016, 11 (7) 1145-1153; DOI: 10.2215/CJN.10210915
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Keywords

  • vitamin D
  • chronic kidney disease
  • vitamin D deficiency
  • vitamin d supplementation
  • albuminuria
  • Child
  • humans
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic
  • 25-hydroxyvitamin D

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