Journal Article

High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease

Wei Ling Lau, Michael Linnes, Emily Y. Chu, Brian L. Foster, Bryan A. Bartley, Martha J. Somerman and Cecilia M. Giachelli

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 28, issue 1, pages 62-69
Published in print January 2013 | ISSN: 0931-0509
Published online October 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs333
High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease

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Background

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear.

Methods

We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice.

Results

In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high–turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification.

Conclusions

HP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice.

Keywords: chronic kidney disease-mineral bone disorder; high-turnover renal osteodystrophy; phosphate; vascular calcification

Journal Article.  4552 words.  Illustrated.

Subjects: Nephrology

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