NDT Advance Access originally published online on November 25, 2005
Nephrology Dialysis Transplantation 2006 21(3):651-659; doi:10.1093/ndt/gfi273
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia
1 Department of Medicine, Division of Hypertension and Nephrology, Kyoto Prefectural University of Medicine, Kyoto, 2 Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe and 3 Product Research Lab, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan
Correspondence and offprint requests to: Masafumi Fukagawa, MD, PhD, FJSIM, FASN, Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan. Email: fukagawa{at}med.kobe-u.ac.jp
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.
Keywords: adenine; calcification; chronic renal failure; hyperparathyroidism; renal osteodystrophy
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