Fortified phosphorus‑lowering treatment through administration of lanthanum protects against vascular calcification via regulation of FGF23 in chronic kidney disease

Jiang,Jie; Li,Yi; Zheng,Dongwen; Wang,Zhen; Zhou,Hongmei; Liu,Guohui

doi:10.3892/ijmm.2020.4719

Fortified phosphorus‑lowering treatment through administration of lanthanum protects against vascular calcification via regulation of FGF23 in chronic kidney disease

Authors:
- Jie Jiang
- Yi Li
- Dongwen Zheng
- Zhen Wang
- Hongmei Zhou
- Guohui Liu
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Affiliations: Nephrology Department, Dongguan People's Hospital Affiliated to Southern Medical University, Dongguan, Guangdong 523059, P.R. China
Published online on: September 4, 2020 https://doi.org/10.3892/ijmm.2020.4719
Pages: 1783-1793
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Phosphorus reduction can prevent against vascular calcification (VC) in chronic kidney disease (CKD), but the mechanisms underlying its actions remain unclear. The aim of the present study was to determine the effect of a fortified phosphorus‑lowing treatment on VC in CKD. Serum levels of creatinine, blood urea nitrogen (BUN), fibroblast growth factor 23 (FGF23), calcium and phosphorus, and the plasma levels of parathyroid hormone (PTH) were determined in an animal model of CKD treated with or without lanthanum. Haematoxylin and eosin (H&E) staining was performed to examine the structure of kidney tissues. Western blot analysis was performed to compare the levels of total‑ (t‑) extracellular signal‑related kinase (ERK) and phospho‑ (p‑)ERK among the different experimental groups to investigate the effect of FGF23 on p‑ERK expression. In the animal model, administration of adenine increased the serum levels of creatinine, BUN, FGF23 and phosphorus but decreased the serum levels of calcium. In addition, adenine treatment increased the plasma levels of PTH. H&E staining showed that lanthanum treatment did not alter the severity of renal cortex injury. Furthermore, the levels of t‑ERK levels did not notably differ between the Adenine‑free, Adenine‑vehicle and Adenine‑lanthanum groups, whereas the levels of p‑ERK and aortic calcium in the Adenine‑vehicle group were significantly upregulated. In addition, ectopic overexpression of FGF23 increased the levels of p‑ERK, Msx2 and Osx in a dose‑dependent manner. Furthermore, a total of 48 patients were enrolled in the present study. In the fortified group, the serum levels of FGF23, phosphorus and PTH were significantly reduced, whereas the serum levels of calcium were significantly increased, indicating an enhanced preventative effect in the fortified group. The results of the present study suggest that FGF23 may be used as a therapeutic target in the management and prevention of VC in CKD.

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