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

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


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.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Adenine / administration & dosage
  • Administration, Oral
  • Animals
  • Blood Urea Nitrogen
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use
  • Creatinine / blood
  • Diet
  • Disease Models, Animal*
  • Disease Progression
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / etiology*
  • Hyperphosphatemia / prevention & control
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / chemically induced
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / drug therapy
  • Male
  • Nephrectomy / methods
  • Phosphorus / blood
  • Polyamines / pharmacology
  • Polyamines / therapeutic use
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Sevelamer
  • Time Factors
  • Up-Regulation


  • Chelating Agents
  • Polyamines
  • Phosphorus
  • Sevelamer
  • Creatinine
  • Adenine