title: Impact of phosphorus restriction and vitamin D-substitution on secondary hyperparathyroidism in a proteinuric mouse model.
abstract: OBJECTIVE
  Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill defined.
  
  
  METHODS
  We investigated the development of SHPT in a doxorubicin-induced proteinuric mouse model and tested different treatment strategies including a low phosphorus diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type mice.
  
  
  RESULTS
  Development of SHPT at day 30 was strongly related to the magnitude of induced proteinuria. In mice with a proteinuria <100 mg/mg creatinine, SHPT was mild (PTH increase 2.4-fold), and serum levels of FGF23, phosphate and urea remained almost stable, whereas mice with heavy proteinuria (>100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold) accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both 25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin D was unable to suppress SHPT, whereas a low-phosphorus diet (Pi content 0.013%) completely suppressed SHPT in mice with both mild and heavy proteinuria.
  
  
  CONCLUSIONS
  The development of SHPT resulted from phosphate retention in this proteinuric model and could completely be suppressed with a low-phosphorus diet.
authors: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen Germany.
authors: Bernhard N
authors: BN
authors: Bohnert
authors: Christoph
authors: C
authors: Daniel
authors: Kerstin
authors: K
authors: Amann
authors: Jakob
authors: J
authors: Voelkl
authors: Ioana
authors: I
authors: Alesutan
authors: Florian
authors: F
authors: Lang
authors: Nils
authors: N
authors: Heyne
authors: Hans-Ulrich
authors: HU
authors: Häring
authors: Ferruh
authors: F
authors: Artunc
mesh_terms: D000818:Animals; D004317:Doxorubicin; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics; D006962:Hyperparathyroidism, Secondary / Q000139:chemically induced / Q000178:diet therapy* / Q000188:drug therapy*; D007668:Kidney / Q000473:pathology; D000090265:Klotho Proteins; D051379:Mice; D010758:Phosphorus; D011507:Proteinuria / Q000139:chemically induced / Q000178:diet therapy* / Q000209:etiology; D051437:Renal Insufficiency / Q000517:prevention & control; D014807:Vitamin D / Q000627:therapeutic use*; D065668:Vitamin D3 24-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: C000717428:Fgf23 protein, mouse; D014815:Vitamins; D014807:Vitamin D; D010758:Phosphorus; D000089703:Fibroblast Growth Factor-23; D004317:Doxorubicin; C585550:Cyp24a1 protein, mouse; D065668:Vitamin D3 24-Hydroxylase; D005966:Glucuronidase; D000090265:Klotho Proteins