title: High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease.
abstract: 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.
authors.affiliation: Department of Nephrology, University of Washington, Seattle, WA, USA.
authors.forename: Wei Ling
authors.initials: WL
authors.lastname: Lau
authors.forename: Michael
authors.initials: M
authors.lastname: Linnes
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chu
authors.forename: Brian L
authors.initials: BL
authors.lastname: Foster
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Bartley
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Somerman
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Giachelli
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001847:Bone Diseases / Q000473:pathology / Q000503:physiopathology*; D001842:Bone and Bones / Q000473:pathology* / Q000503:physiopathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000503:physiopathology*; D005260:Female; D051379:Mice; D008811:Mice, Inbred DBA; D010710:Phosphates / Q000008:administration & dosage*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology*; D061205:Vascular Calcification / Q000503:physiopathology*
chemical_list: D010710:Phosphates