title: Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia.
abstract: BACKGROUND
  Marked parathyroid hyperplasia with bone diseases and vascular calcification are unsolved issues in dialysis patients. In this study, we made azotemic model rats by adenine feeding and analyzed the development and progression of the abnormalities.
  
  
  METHODS
  Renal failure was induced in 8-week-old male Wistar rats by feeding 0.75% adenine-containing diet for 6 weeks. Serum parameters, parathyroid hyperplasia, bone changes and metastatic calcification were examined at 2, 4 and 6 weeks.
  
  
  RESULTS
  Progressive increase of serum creatinine and inorganic phosphate, and decreased levels of serum calcium and 1,25(OH)2D3 were confirmed. Markedly enlarged parathyroid glands and extremely high PTH levels were observed in all adenine-fed rats compared with the control (PTH: 199.3+/-58.0 vs 10.5+/-3.0 pmol/l, P<0.01, respectively, at 6 weeks). In cortical bone of the femur, the morphometric parameters showed increased bone resorption with increased fibrosis, whereas in the trabecular bone, bone resorption decreased and bone volume increased with a larger amount of osteoid compared with the control. Metastatic calcification in aorta, coronary artery and other soft tissues were also found in adenine-fed rats.
  
  
  CONCLUSIONS
  Uraemic rats made by adenine diet developed severe abnormalities of calcium metabolism in a relatively short period and therefore they may serve as a useful model for the analysis of parathyroid hyperplasia and vascular calcification in chronic renal failure.
authors.affiliation: Division of Hypertension and Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamagaki
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Yuan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohkawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Imazeki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Moriguchi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Imai
authors.forename: Susumu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000225:Adenine / Q000633:toxicity; D000818:Animals; D001018:Aortic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001806:Blood Urea Nitrogen; D002114:Calcinosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005269:Femur / Q000473:pathology; D005500:Follow-Up Studies; D006961:Hyperparathyroidism / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D008852:Microradiography; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014511:Uremia / Q000139:chemically induced / Q000150:complications* / Q000473:pathology
chemical_list: D010281:Parathyroid Hormone; D003404:Creatinine; D002117:Calcitriol; D000225:Adenine; D002118:Calcium