BACKGROUND: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress.
METHODS: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein).
RESULTS: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function.
CONCLUSIONS: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.
Bibliographical noteFunding Information:
A.B. has received honoraria from Amgen. S.M.M. has received grant funding from Amgen, Sanofi, Chugai, and Keryx and scientific advising fees from Amgen. All other authors have no conflicts of interest to declare.
A.B. was supported by the National Institutes of Health T32AR065971. KMHG was supported by NIH K01DK102864. S.M.M. has received grant funding from Amgen, Sanofi, Chugai, and Keryx and scientific advising fees from Amgen and is supported by the Veterans Affairs Merit Award BX001471, and NIH R01DK11087103, P30AR072581. Purdue University rat data were from a study partially funded through a Showalter Research Trust award to K.M.H.G. Part of the results in this paper were presented at Kidney Week 2019.
© 2020 S. Karger AG, Basel.
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