Assessment of a Novel Phosphate Binding Therapy in Experimental Adenine-Induced Chronic Kidney Disease

dc.contributor.authorJeronimo, Paulen
dc.contributor.departmentBiomedical and Molecular Sciencesen
dc.contributor.supervisorAdams, Michaelen
dc.contributor.supervisorHolden, Rachelen's University at Kingstonen
dc.description.abstractHyperphosphatemia 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.en
dc.embargo.termsThe thesis needs to remain confidential due to both publication issues as well as a disclosure arrangement with OPKO Health. All parties want the work to be published but after appropriate review and opportunity for feedback.en
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
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dc.subjectVascular Calcificationen
dc.subjectChronic Kidney Diseaseen
dc.subjectPhosphate Binderen
dc.titleAssessment of a Novel Phosphate Binding Therapy in Experimental Adenine-Induced Chronic Kidney Diseaseen
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