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      Adverse Effects of Autoclaved Diets on the Progression of Chronic Kidney Disease and Chronic Kidney Disease-Mineral Bone Disorder in Rats


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          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.

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          Author and article information

          Am J Nephrol
          American Journal of Nephrology
          S. Karger AG
          May 2020
          06 March 2020
          : 51
          : 5
          : 381-389
          [_a] aDivision of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
          [_b] bDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
          [_c] cDepartment of Applied Health Science, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana, USA
          [_d] dDepartment of Nutrition Science, Purdue University, West Lafayette, Indiana, USA
          [_e] eDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
          [_f] fLaboratory Animal Resource Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
          [_g] gRoudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA
          Author notes
          *Sharon M. Moe, MD, Division of Nephrology, Indiana University School of Medicine, 950 W Walnut Street, R2-202, Indianapolis, IN 46202 (USA), smoe@iu.edu
          506729 Am J Nephrol 2020;51:381–389
          © 2020 S. Karger AG, Basel

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          Page count
          Figures: 3, Tables: 1, Pages: 9
          Laboratory Investigation: Research Article


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