Assessment of a Novel Phosphate Binding Therapy in Experimental Adenine-Induced Chronic Kidney Disease
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Authors
Jeronimo, Paul
Date
Type
thesis
Language
eng
Keyword
Vascular Calcification , Chronic Kidney Disease , Phosphate Binder , Magnesium
Alternative Title
Abstract
Hyperphosphatemia is a hallmark of progression in chronic kidney disease (CKD) and has been linked to the development of vascular calcification (VC), which increases cardiovascular risk. Phosphate binders are prescribed to control hyperphosphatemia. Fermagate is a calcium-free, magnesium-releasing, phosphate binder. Oral delivery of magnesium has been shown to attenuate VC. The aim of this study was to determine whether fermagate treatment compared to no treatment could impact VC in male Sprague-Dawley rats using an experimental model of adenine-induced CKD. The effect of fermagate on two different high phosphate dietary regimens was performed: high phosphate (0.75%) diet at all meals or a combination of low (0.5%) and high (1%) phosphate meals, such that the total amount of phosphate delivered was the same. In both studies, administration of fermagate increased serum magnesium and attenuated the levels of circulating phosphate, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23). Compared to untreated CKD rats, fermagate treatment significantly reduced the prevalence of VC across a range of vascular tissues (70% VC in treated vs. 24% VC in untreated), but did not alter the accrual of magnesium in the vasculature. Serum phosphate and the prevalence of VC were higher in untreated and fermagate-treated rats on the constant high (0.75%) diet compared to the combination diet (0.5/1%), suggesting the impact of phosphate is dependent on the delivery of phosphate, not only the amount of phosphate consumed. Overall, the findings demonstrate that fermagate effectively reduces the bioavailability of the dietary phosphate load, increases systemic levels of magnesium, and limits the development and progression of CKD and VC.
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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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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.
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.