Background: Adenine at 0.75% in the diet (AD) triggers renal impairment in rats. This model of kidney disease is largely reversible when AD feeding is stopped. Testing of novel drugs parallel to AD administration may result in unwanted interference.
Objectives: We hypothesized that combining AD with unilateral nephrectomy (UNx) would result in progressive chronic kidney disease (CKD) even after cessation of AD.
Methods: In an explorative study, 16 rats with UNx (AD-1K rats) and 10 sham-operated rats (AD-2K rats) received AD-supplemented feed for 3 weeks, followed by 4 weeks of standard chow. Ten sham-operated rats receiving only standard chow served as controls. Laboratory parameters in blood and urine were frequently assessed during and after cessation of AD feeding. Comprehensive pathological examinations were performed in all rats at the end of the experiment.
Results: Rats with UNx were more affected by impaired glomerular filtration rate, anemia, hyperphosphatemia, and hypocalcemia. After cessation of AD feeding, recovery was poorest in AD-1K rats, paralleled by increased proteinuria indicative of progressive CKD. Scores in histopathological damage of the kidneys indicative of CKD were seen in both AD-fed groups, with key parameters being more affected in AD-1K rats. Histopathological changes in the heart were most prominent in AD-1K rats.
Conclusions: Combining AD feeding with UNx provides a time window after cessation of AD feeding for the testing of drugs without interference. Our findings in rats may have implications for research in other target animal species as well.
Keywords: Adenine; Chronic kidney disease model; Glomerular filtration rate; Rat; Unilateral nephrectomy.