title: Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels.
abstract: OBJECTIVE
  Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis.
  
  
  METHODS
  Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined.
  
  
  RESULTS
  After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated.
  
  
  CONCLUSIONS
  These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.
authors.affiliation: Diabetic Complications Department, Pharmacology Research Lab., Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. kazuhiro.terai@jp.astellas.com
authors.forename: K
authors.initials: K
authors.lastname: Terai
authors.forename: H
authors.initials: H
authors.lastname: Nara
authors.forename: K
authors.initials: K
authors.lastname: Takakura
authors.forename: K
authors.initials: K
authors.lastname: Mizukami
authors.forename: M
authors.initials: M
authors.lastname: Sanagi
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.forename: A
authors.initials: A
authors.lastname: Fujimori
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: M
authors.initials: M
authors.lastname: Okada
mesh_terms: D000225:Adenine; D000818:Animals; D001018:Aortic Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002114:Calcinosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D002118:Calcium / Q000097:blood*; D002119:Calcium Carbonate / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002762:Cholecalciferol / Q000494:pharmacology; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D054559:Hyperphosphatemia / Q000097:blood / Q000209:etiology; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood*; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000069603:Sevelamer; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D002762:Cholecalciferol; D000069603:Sevelamer; D003404:Creatinine; D002119:Calcium Carbonate; D000225:Adenine; D002118:Calcium