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High-serum phosphate and parathyroid hormone distinctly regulate bone loss and vascular calcification in experimental chronic kidney disease.

Authors
  • Carrillo-López, Natalia1
  • Panizo, Sara1
  • Alonso-Montes, Cristina1
  • Martínez-Arias, Laura1
  • Avello, Noelia2
  • Sosa, Patricia3
  • Dusso, Adriana S1
  • Cannata-Andía, Jorge B1, 4
  • Naves-Díaz, Manuel1
  • 1 Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain. , (Spain)
  • 2 Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain. , (Spain)
  • 3 Departamento de Biología de Sistemas, Universidad de Alcalá, REDinREN-ISCIII, Alcalá de Henares, Spain. , (Spain)
  • 4 Departamento de Medicina, Universidad de Oviedo, Oviedo, Spain. , (Spain)
Type
Published Article
Journal
Nephrology Dialysis Transplantation
Publisher
Oxford University Press
Publication Date
Jun 01, 2019
Volume
34
Issue
6
Pages
934–941
Identifiers
DOI: 10.1093/ndt/gfy287
PMID: 30189026
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In chronic kidney disease (CKD), increases in serum phosphate and parathyroid hormone (PTH) aggravate vascular calcification (VC) and bone loss. This study was designed to discriminate high phosphorus (HP) and PTH contribution to VC and bone loss. Nephrectomized rats fed a HP diet underwent either sham operation or parathyroidectomy and PTH 1-34 supplementation to normalize serum PTH. In uraemic rats fed a HP diet, parathyroidectomy with serum PTH 1-34 supplementation resulted in (i) reduced aortic calcium (80%) by attenuating osteogenic differentiation (higher α-actin; reduced Runx2 and BMP2) and increasing the Wnt inhibitor Sclerostin, despite a similar degree of hyperphosphataemia, renal damage and serum Klotho; (ii) prevention of bone loss mostly by attenuating bone resorption and increases in Wnt inhibitors; and (iii) a 70% decrease in serum calcitriol levels despite significantly reduced serum Fgf23, calcium and renal 24-hydroxylase, which questions that Fgf23 is the main regulator of renal calcitriol production. Significantly, when vascular smooth muscle cells (VSMCs) were exposed exclusively to high phosphate and calcium, high PTH enhanced while low PTH attenuated calcium deposition through parathyroid hormone 1 receptor (PTH1R) signalling. In hyperphosphataemic CKD, a defective suppression of high PTH exacerbates HP-mediated osteogenic VSMC differentiation and reduces vascular levels of anti-calcifying sclerostin. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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