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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Mini-Review Article

Phosphate Toxicity and Vascular Calcification in Chronic Kidney Disease: A Closer Look Utilizing Transmission Electron Microscopy

Author(s): Ying Yang*, Ke Yang, Yuxin Xiong, Yusong He, Yuanyuan Zhou and Melvin R. Hayden*

Volume 24, Issue 8, 2023

Published on: 15 August, 2023

Page: [621 - 639] Pages: 19

DOI: 10.2174/1389203724666230726151019

Price: $65

Abstract

Hyperphosphatemia is independently linked with vascular calcification, cardiovascular disease, bone-mineral disease, progression of renal insufficiency, and all-cause mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD). The emerging importance of fibroblast growth factor-23 (FGF-23) and its co-factor Klotho play very important roles as phosphaturic hormones; however, phosphate levels rise due to a loss of renal Klotho production and the phosphaturic effects of the FGF-23/Klotho axis. Hyperphosphatemia is also associated with calciphylaxis, acceleration of renal tubulointerstitial disease, renal osteodystrophy, and uremic cardiomyopathy. This review incorporates ultrastructural remodeling of the thoracic aorta to provide a different perspective on vascular calcification. Nine-week-old male heterozygous (mRen2) 27 (Ren2) rat models of hypertension, insulin resistance, vascular oxidative stress and albuminuria are utilized to demonstrate aortic remodeling associated with vascular calcification. Nine-week-old male Zucker obese (fa/fa) rat models are utilized to better understand nephrolith formation. Phosphate homeostasis, toxicity, multiple metabolic and uremic toxicities, renal osteodystrophy, and vascular calcification are also discussed. Additionally, the role of the endothelium, vascular smooth muscle cells, inflammatory monocytes/macrophages and mast cells, pericytes, oxidative stress, hydrogen sulfide, and extraosseous calcification in the kidney are discussed as they relate to CKD, ESRD and calciphylaxis.

Keywords: Aorta, chronic kidney disease, endothelium, hyperphosphatemia, vascular calcification, ultrastructure.

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Graphical Abstract

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