Article ; Online: Interactions of vitamin D and the proximal tubule.
Pediatric nephrology (Berlin, Germany)
2015 Volume 31, Issue 1, Page(s) 7–14
Abstract: Severe vitamin D deficiency (reduction in serum 25(OH)D concentration) in infants and children can cause features of the Fanconi syndrome, including phosphaturia, glycosuria, aminoaciduria, and renal tubular acidosis. This indicates that vitamin D and ... ...
| Abstract | Severe vitamin D deficiency (reduction in serum 25(OH)D concentration) in infants and children can cause features of the Fanconi syndrome, including phosphaturia, glycosuria, aminoaciduria, and renal tubular acidosis. This indicates that vitamin D and its metabolites influence proximal tubule function. Filtered 25(OH)D bound to vitamin D binding protein (DBP) is endocytosed by megalin-cubilin in the apical membrane. Intracellular 25(OH)D is metabolized to 1,25(OH)2D or calcitroic acid by 1-α-hydroxylase or 24-hydroxylase in tubule cell mitochondria. Bone-produced fibroblast growth factor 23 (FGF23) bound to Klotho in tubule cells and intracellular phosphate concentrations are regulators of 1-α-hydroxylase activity and cause proximal tubule phosphaturia. Aminoaciduria occurs when amino acid transporter synthesis is deficient, and 1,25(OH)2D along with retinoic acid up-regulate transporter synthesis by a vitamin D response element in the promoter region of the transporter gene. This review discusses evidence gained from studies in animals or cell lines, as well as from human disorders, that provide insight into vitamin D-proximal tubule interactions. |
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| MeSH term(s) | 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Animals ; Genetic Predisposition to Disease ; Humans ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/physiopathology ; Low Density Lipoprotein Receptor-Related Protein-2/genetics ; Low Density Lipoprotein Receptor-Related Protein-2/metabolism ; Prognosis ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Renal Aminoacidurias/etiology ; Renal Aminoacidurias/genetics ; Renal Aminoacidurias/metabolism ; Renal Aminoacidurias/physiopathology ; Risk Factors ; Signal Transduction ; Vitamin D/metabolism ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/genetics ; Vitamin D Deficiency/metabolism ; Vitamin D Deficiency/physiopathology ; Vitamin D3 24-Hydroxylase/genetics ; Vitamin D3 24-Hydroxylase/metabolism |
| Chemical Substances | LRP2 protein, human ; Low Density Lipoprotein Receptor-Related Protein-2 ; Receptors, Calcitriol ; Receptors, Cell Surface ; VDR protein, human ; intrinsic factor-cobalamin receptor ; Vitamin D (1406-16-2) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.13.13) ; CYP24A1 protein, human (EC 1.14.15.16) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16) ; CYP27B1 protein, human (EC 1.14.15.18) |
| Language | English |
| Publishing date | 2015-01-25 |
| Publishing country | Germany |
| Document type | Journal Article ; Review |
| ZDB-ID | 631932-4 |
| ISSN | 1432-198X ; 0931-041X |
| ISSN (online) | 1432-198X |
| ISSN | 0931-041X |
| DOI | 10.1007/s00467-015-3050-5 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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