title: Interactions of vitamin D and the proximal tubule.
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.
authors.affiliation: Department of Pediatrics, The University of Tennessee Health Science Center, and the Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN, USA. rchesney@uthsc.edu.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Chesney
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000089703:Fibroblast Growth Factor-23; D020022:Genetic Predisposition to Disease; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000608:Renal Aminoacidurias / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors; D015398:Signal Transduction; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D018167:Receptors, Calcitriol; D011956:Receptors, Cell Surface; C579457:VDR protein, human; C029486:intrinsic factor-cobalamin receptor; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human
keywords: Aminoaciduria; Cubilin; FGF23; Klotho; Megalin; Taurinuria; Vitamin D deficiency