Chronic kidney disease induced by adenine: a suitable model of growth retardation in uremia

Abstract

Growth retardation is a major manifestation of chronic kidney disease (CKD) in pediatric patients. The involvement of the various pathogenic factors is difficult to evaluate in clinical studies. Here, we present an experimental model of adenine-induced CKD for the study of growth failure. Three groups (n = 10) of weaning female rats were studied: normal diet (control), 0.5% adenine diet (AD), and normal diet pair fed with AD (PF). After 21 days, serum urea nitrogen, creatinine, parathyroid hormone (PTH), weight and length gains, femur osseous front advance as an index of longitudinal growth rate, growth plate histomorphometry, chondrocyte proliferative activity, bone structure, aorta calcifications, and kidney histology were analyzed. Results are means ± SE. AD rats developed renal failure (serum urea nitrogen: 70 ± 6 mg/dl and creatinine: 0.6 ± 0.1 mg/dl) and secondary hyperparathyroidism (PTH: 480 ± 31 pg/ml). Growth retardation of AD rats was demonstrated by lower weight (AD rats: 63.3 ± 4.8 g, control rats: 112.6 ± 4.7 g, and PF rats: 60.0 ± 3.8 g) and length (AD rats: 7.2 ± 0.2 cm, control rats: 11.1 ± 0.3 cm, and PF rats: 8.1 ± 0.3 cm) gains as well as lower osseous front advances (AD rats: 141 ± 13 μm/day, control rats: 293 ± 16 μm/day, and PF rats: 251 ± 10 μm/day). The processes of chondrocyte maturation and proliferation were impaired in AD rats, as shown by lower growth plate terminal chondrocyte height (21.7 ± 2.3 vs. 26.2 ± 1.9 and 23.9 ± 1.3 μm in control and PF rats) and proliferative activity index (AD rats: 30 ± 2%, control rats: 38 ± 2%, and PF rats: 42 ± 3%). The bone primary spongiosa structure of AD rats was markedly disorganized. In conclusion, adenine-induced CKD in young rats is associated with growth retardation and disturbed endochondral ossification. This animal protocol may be a useful new experimental model to study growth in CKD.

Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease

“…3 Additionally, in patients with primary hyperparathyroidism, lumbar vertebral bone mineral content was reported to be increased, whereas bone mineral density of the radius was found to be decreased. 21 Furthermore, increases in tibial and femoral trabecular BV/TV have been reported in mouse 19,20 and rat 22,23 models of kidney disease with secondary hyperparathyroidism as well as in vertebrae of rats treated with continuous PTH infusions. 24 These reports support the impression that in the model reported here, hyperparathyroidism led to the observed bone phenotype.…”

iTRAQ‐Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha‐1‐Antitrypsin as Potential Biomarkers

“…The control group was fed standard chow, while the other two groups were fed 0.5% adenine (Sigma-Aldrich, St. Louis, MO, USA) chow for 3 weeks to induce chronic renal failure [37, 38]. After the models were successfully made, rats in control and model groups received saline in the amount of 20 ml/kg/d, while those in FSGD group received 16 g/kg/d, administered by gastric irrigation, respectively, for 30 days.…”

Adenine‐induced chronic kidney disease in rats

“…The 0.25% adenine diet was also used as a model for CKD in mice either for 10 days or for 4 weeks . Another study demonstrated similar CKD responses, however, with a higher (0.5%) dose of adenine for 3 weeks which approximates to only 1.5 years in humans . Kidney disease was established with 0.2% adenine for 4 weeks in C57 BL6 mice .…”