Characterizing the Impact of Dietary Mineral Intake on Secondary Hyperparathyroidism, Vascular Calcification, and Bone Disease Within Experimental Chronic Kidney Disease
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Authors
Lansing, Austin
Date
Type
thesis
Language
eng
Keyword
Chronic kidney disease , Secondary hyperparathyroidism , CKD-MBD , Dietary mineral intake
Alternative Title
Abstract
Chronic kidney disease (CKD) affects an estimated 25 million North Americans and is a significant risk factor for cardiovascular disease (CVD) and overall mortality. This is largely a result of systemic dysregulation in mineral metabolism, termed CKD-mineral bone disorder (CKD-MBD). The aim of this study was to investigate how elevated dietary phosphate (PO4), and further, the resulting decreases in the ratio of calcium (Ca)-to- PO4, contribute to key cardiovascular disease risk factors: mineral bone disorder pathology and secondary hyperparathyroidism. Male rats had CKD induced using dietary adenine, and then were either sacrificed after induction, or challenged with a 12-day dietary intervention. 4 diets were used, assessing a combination of high vs low dietary PO4, and Ca-to-PO4 ratio. All 5 CKD groups, in addition to healthy control animals, were compared with respect to serum mineral and hormone levels, bone microarchitecture, VC, and ex vivo parathyroid gland responsiveness. For each parameter tested, all 5 CKD groups were shown to be significantly different from controls, with 12 days of dietary intervention producing further changes. Despite similar levels of VC between dietary intervention groups, mineral content of the dietary intervention was shown to have an impact on serum parameters, with low dietary Ca:PO4 ratio, as well as high dietary PO4, regardless of ratio, producing significant elevations in parathyroid hormone and circulating P relative to animals fed normal PO4 with normal ratio. Normal PO4 with normal ratio was also shown to be protective against bone loss, with low ratio and high PO4 groups showing greater loss. Overall, the findings show that compared to the other diets tested, normal dietary PO4 with normal Ca:PO4 ratio is associated with improved outcomes within CKD. Increasing dietary PO4, regardless of ratio, as well as lowering the ratio through reductions in Ca, exacerbates the abnormalities in mineral metabolism which develop within CKD and are associated with overall poor clinical outcomes, CVD, and high risk of mortality.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal