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Nephrology (Carlton). 2008 Apr;13(2):139-46. doi: 10.1111/j.1440-1797.2007.00844.x.

Comparison of chronic renal failure rats and modification of the preparation protocol as a hyperphosphataemia model.

Author information

1
Kidney and Digestive Tracts Laboratory, Institute of Pharmacology, Astellas Pharma Co. Ltd, Miyukigaoka, Tsukuba, Ibaraki, Japan. kazuhiro.terai@jp.astellas.com

Abstract

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.

CONCLUSION:

Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev.

[Indexed for MEDLINE]

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