Age-related differences in the skeletal phenotype of Brown Norway rats induced to develop chronic kidney disease.

Abstract

A large proportion of the chronic kidney disease (CKD) population is over the age of 65 with age being a significant factor increasing fracture incidence in CKD. However, the interactions of aging and CKD on the skeleton remain unclear in part due to limited pre-clinical models to study the intersection of aging and CKD. In the current study, we aimed to define age-related differences in the skeletal manifestations of CKD using an adenine-induction model in young (3-month-old) and aging (17-month-old) Brown Norway rats. We hypothesized that there would be a greater CKD-Mineral Bone Disorder phenotype in aging rats compared to young rats. Serum blood urea nitrogen, creatinine, and parathyroid hormone were higher in aging CKD rats compared to young. Bone turnover was high in all CKD rats, but osteoclast-covered trabecular surfaces were highest in aging CKD. Additionally, osteoid surfaces and osteoid width were only elevated in aging adenine rats. Cortical porosity was only present in the aging cohort and elevated due to CKD. A marker of cellular senescence was elevated in cortical osteocytes due to both CKD and aging. Parathyroid hormone receptor 1 (PTHR1) was elevated due to CKD only in young CKD rats. In conclusion, this study demonstrates that aging rodents develop a more severe CKD-MBD phenotype than young rodents with higher osteoclasts, elevated osteoid, and greater cortical porosity. These data highlight both a pre-clinical model suitable to study age-related CKD and that CKD-induced skeletal changes have age-specific effects.