Comparison of chronic renal failure rats and modification of the preparation protocol as a hyperphosphataemia model.
BACKGROUND
Several animal models with chronic renal failure have been established and used for demonstrating complications including hyperphosphataemia. Although long-time feeding is required to cause hyperphosphataemia in animals, a few modifications have been reported to provide more useful models for research.


METHODS
Three separate experiments were carried out in the present study. First, characteristics of commonly used subnephrectomized (5/6Nx) rats and rats fed an adenine diet (0.75% adenine in normal diet) were compared as hyperphosphataemia models. Next, using adenine-diet rats, the inhibitory effect of sevelamer hydrochloride (Sev) on serum phosphorus elevation was examined. Third, oral adenine dosing for induction of hyperphosphataemia and validation as a model using Sev were examined.


RESULTS
Serum phosphorus in 5/6Nx rats became elevated in 8-17 weeks, but the levels and time points of elevation differed among animals. In adenine-fed rats, the elevation was more clearly demonstrated with less diversity at 4 weeks. The data revealed a potential shorter model preparation period and the importance of controlling feeding amounts. Oral adenine dosing induced hyperphosphataemia by 12 days, and Sev treatment was inhibitory. After a maintenance period of over a month (no treatments), Sev-treated rats showed hyperphosphataemia as did oral adenine-dosed control rats. The serum phosphorus levels significantly decreased on further Sev treatment.


CONCLUSIONS
Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev.
Terai
Kazuhiro
K
Kidney and Digestive Tracts Laboratory, Institute of Pharmacology, Astellas Pharma Co. Ltd, Miyukigaoka, Tsukuba, Ibaraki, Japan. kazuhiro.terai@jp.astellas.com
Mizukami
Kazuhiko
K
Okada
Masamichi
M
D000225:Adenine / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D001806:Blood Urea Nitrogen; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D054559:Hyperphosphatemia / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D008297:Male; D009392:Nephrectomy / Q000379:methods; D010758:Phosphorus / Q000097:blood; D011073:Polyamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D000069603:Sevelamer; D013997:Time Factors; D015854:Up-Regulation
D002614:Chelating Agents; D011073:Polyamines; D010758:Phosphorus; D000069603:Sevelamer; D003404:Creatinine; D000225:Adenine