A High Fat/High Sucrose Diet Alters the Skeletal Response to Adenine-Induced Chronic Kidney Disease in Male Rats.

Abstract

Chronic kidney disease (CKD) impacts a large and growing proportion of the population. Fracture rates are high in individuals with CKD compared to the non-CKD population. Dietary patterns consisting of higher fat and sugar intake are associated with higher risk of developing CKD, but the impact of different dietary patterns on the skeleton in the setting of CKD is largely unknown. To assess the impact of a high fat/high sucrose diet (HFHS) in male Sprague Dawley rats with adenine-induced CKD (Ad). Rats were given the HFHS or standard diet (SD) for 4 weeks followed by 8 weeks with adenine incorporated into those diets for the Ad groups. All Ad rats, regardless of diet, had high circulating blood urea nitrogen and parathyroid hormone (PTH). Ad + SD rats had greater femoral volumetric cortical porosity and pore number and lower mechanical properties than Ad + HFHS rats. Ad + HFHS had a lower percentage of cortical bone osteocytes positive for PTHR1 and RANKL matching trends in porosity; however, the HFHS diet led to greater TNF-α-positive osteocytes and trabecular osteoclast numbers. There were differences in the skeletal response to adenine-induced CKD based on diet with the standard diet leading to a skeletal phenotype more associated with high PTH. These data demonstrate both the complexity of systemic alterations impacting bone in CKD and highlight the importance of understanding the influence of dietary factors on skeletal outcomes.