title: Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification.
abstract: OBJECTIVE
  Ferric citrate hydrate (JTT-751) is being developed as a treatment for hyperphosphatemia in chronic kidney disease patients, and shows serum phosphorus-reducing effects on hyperphosphatemia in hemodialysis patients. We examined whether JTT-751 could reduce phosphorus absorption in normal rats and prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in chronic renal failure (CRF) rats.
  
  
  METHODS
  Normal rats were fed a diet containing 0.3, 1 or 3% JTT-751 for 7 days. The effects of JTT-751 on phosphorus absorption were evaluated with fecal and urinary phosphorus excretion. Next, a CRF model simulating hyperphosphatemia was induced by feeding rats a 0.75% adenine diet. After 21 days of starting the adenine diet feeding, 1 or 3% JTT-751 was administered for 35 days by dietary admixture. The serum phosphorus levels and mineral parameters were measured. Calcification in the aorta was examined biochemically and histopathologically. Hyperparathyroidism and bone abnormalities were evaluated by histopathological analysis of the parathyroid and femur, respectively.
  
  
  RESULTS
  In normal rats, JTT-751 increased fecal phosphorus excretion and reduced phosphorus absorption and urinary phosphorus excretion. In CRF rats, JTT-751 reduced serum phosphorus levels, the calcium-phosphorus product and calcium content in the aorta. Serum intact parathyroid hormone levels and the incidence and severity of parathyroid hyperplasia were also decreased. JTT-751 reduced femoral bone fibrosis, porosity and osteoid formation.
  
  
  CONCLUSIONS
  JTT-751 could bind with phosphate in the gastrointestinal tract, increase fecal phosphorus excretion and reduce phosphorus absorption. JTT-751 could prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in rats.
authors.affiliation: Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Japan. akio.ida@jt.com
authors.forename: Akio
authors.initials: A
authors.lastname: Iida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kemmochi
authors.forename: Kochi
authors.initials: K
authors.lastname: Kakimoto
authors.forename: Minako
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mimura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Uemura
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuo
authors.forename: Mutsuyoshi
authors.initials: M
authors.lastname: Matsushita
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology*; D006962:Hyperparathyroidism, Secondary / Q000473:pathology / Q000517:prevention & control*; D054559:Hyperphosphatemia / Q000517:prevention & control; D008297:Male; D010280:Parathyroid Glands / Q000473:pathology; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D061205:Vascular Calcification / Q000473:pathology / Q000517:prevention & control*
chemical_list: D005290:Ferric Compounds; D010710:Phosphates; C025314:ferric citrate; D002118:Calcium