Analysis of bone in adenine-induced chronic kidney disease model rats

Abstract

Objectives

The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats.

Methods

Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points.

Results

In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone.

Conclusions

These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.