Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia.
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.
Tamagaki
Keiichi
K
Division of Hypertension and Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yuan
Qunsheng
Q
Ohkawa
Hiroyuki
H
Imazeki
Ikuo
I
Moriguchi
Yoshiyuki
Y
Imai
Nobuo
N
Sasaki
Susumu
S
Takeda
Kazuo
K
Fukagawa
Masafumi
M
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
D010281:Parathyroid Hormone; D003404:Creatinine; D002117:Calcitriol; D000225:Adenine; D002118:Calcium