Title:Phosphate Toxicity and Vascular Calcification in Chronic Kidney Disease:
A Closer Look Utilizing Transmission Electron Microscopy
Volume: 24
Issue: 8
Author(s): Ying Yang*, Ke Yang, Yuxin Xiong, Yusong He, Yuanyuan Zhou and Melvin R. Hayden*
Affiliation:
- Department of Endocrinology, the Affiliated Hospital of Yunnan University and the Second People’s Hospital of Yunnan Province, Kunming, Yunnan, 650021, China
- Departments of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri-Columbia School of Medicine, Columbia, Missouri, 65212, USA
- Departments of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri-Columbia School of Medicine, Columbia, Missouri, 65212, USA
Keywords:
Aorta, chronic kidney disease, endothelium, hyperphosphatemia, vascular calcification, ultrastructure.
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.
