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



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.



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.



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.
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
Anke
A
Doyon
Bettina
B
Schmiedchen
Anja
A
Sander
Aysun
A
Bayazit
Ali
A
Duzova
Nur
N
Canpolat
Daniela
D
Thurn
Karolis
K
Azukaitis
Ali
A
Anarat
Justine
J
Bacchetta
Sevgi
S
Mir
Rukshana
R
Shroff
Ebru
E
Yilmaz
Cengiz
C
Candan
Markus
M
Kemper
Michel
M
Fischbach
Gerard
G
Cortina
Günter
G
Klaus
Matthias
M
Wuttke
Anna
A
Köttgen
Anette
A
Melk
Uwe
U
Querfeld
Franz
F
Schaefer
D000293:Adolescent; D000419:Albuminuria / Q000209:etiology; D002648:Child; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005060:Europe; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012621:Seasons; D012737:Sex Factors; D013472:Sunlight; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000097:blood* / Q000235:genetics* / Q000517:prevention & control; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics; D014815:Vitamins / Q000627:therapeutic use
C000625431:24,25-dihydroxyvitamin D; D010281:Parathyroid Hormone; D014809:Vitamin D-Binding Protein; D014815:Vitamins; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D053493:Cholestanetriol 26-Monooxygenase; D065668:Vitamin D3 24-Hydroxylase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
25-hydroxyvitamin D; Child; Humans; Polymorphism, Single Nucleotide; Renal Insufficiency, Chronic; Vitamin D; albuminuria; chronic kidney disease; vitamin D deficiency; vitamin d supplementation