Reversibility of adenine-induced renal failure in rats

Abstract

Background. A renal failure model prepared from rats fed on an adenine diet provides valuable information about the pathomechanism of various complications associated with a persistent uremic state. To establish an animal experimental model in which the animals survive in a persistent uremic state, it is essential to settle a point of no return, i.e., an irreversible point. We investigated an irreversible point using the rat renal failure model induced by adenine treatment.

Methods. Rats were fed on a diet containing 0.75% adenine for 2, 4, or 6 weeks, and they were then fed an adenine-free diet for an additional 4 weeks to evaluate the degree of recovery from renal dysfunction.

Results. The rats fed on the adenine diet for 2 weeks showed a decrease in mean serum creatinine(s-Cr) from 1.8 mg/dl before to 0.7 mg/dl after the observation period, with mild anemia. The rats fed on the adenine diet for 4 weeks showed persistent renal dysfunction. Although the mean s-Cr decreased from 2.7 to 2.0 mg/dl, it continued to be higher than the normal range, and the anemia worsened. In the rats fed on the adenine diet for 6 weeks, the mean s-Cr increased from 3.4 to 3.6 mg/dl. Hypoproteinemia was also observed and some animals died.

Conclusion. Based on the above results, it was concluded that to prepare a model of chronic renal failure in rats compatible to chronic renal failure seen clinically, the administration of a 0.75% adenine diet for 4 weeks is most appropriate.