SUN-351 Sex Is a Strong Variable in the Mineral Metabolism Defects and Endocrine Dysfunction Associated with the Murine Adenine Diet Model of Chronic Kidney Disease (CKD)

Autor: Kenneth E. White, Julia M. Hum, Erica L. Clinkenbeard, Samantha P. Tippen, Rafiou Agoro, Megan L. Noonan, Michael P. Liesen, Pu Ni
Rok vydání: 2020
Předmět:
Zdroj: Journal of the Endocrine Society
ISSN: 2472-1972
DOI: 10.1210/jendso/bvaa046.658
Popis: The adenine diet is widely used in animal models to produce a tubulointerstitial fibrosis and inflammation that mimics human CKD in many aspects. These include the biochemical manifestations hyperphosphatemia and anemia, as well as endocrine dysfunction with elevated FGF23 and hyperparathyroidism. Male rodents are known to be less tolerant of adenine diet regimen than females, however the underlying mechanisms driving the sex differences remain unclear. Additionally, much of the data for adenine studies arises from rats, whereas mice are more commonly used in laboratory settings and are far easier to manipulate genetically. To this end, as part of a larger study to test the effects of iron-handling in CKD, we assessed the biochemical, molecular, and physical differences between male and female mice receiving an adenine diet to induce CKD. Flox-Fgf23 mice (8 weeks of age, n=4-6/group; mice were Cre negative, thus phenotypically wild type) were placed on a 0.2% adenine-containing diet (CKD); a matching casein-based diet served as control. After 6 weeks, mice were euthanized, and blood and tissues were collected for analysis. As expected, body weight at baseline was initially higher in males than in females, however males lost significantly more weight. Serum BUN was also elevated in both sexes receiving adenine, although males were higher (1.2 fold; p
Databáze: OpenAIRE