title: Can Intestinal Phosphate Binding or Inhibition of Hydroxyapatite Growth in the Vascular Wall Halt the Progression of Established Aortic Calcification in Chronic Kidney Disease?
abstract: Vascular calcification significantly contributes to mortality in chronic kidney disease (CKD) patients. Sevelamer and pyrophosphate (PPi) have proven to be effective in preventing vascular calcification, the former by controlling intestinal phosphate absorption, the latter by directly interfering with the hydroxyapatite crystal formation. Since most patients present with established vascular calcification, it is important to evaluate whether these compounds may also halt or reverse the progression of preexisting vascular calcification. CKD and vascular calcification were induced in male Wistar rats by a 0.75 % adenine low protein diet for 4 weeks. Treatment with PPi (30 or 120 µmol/kg/day), sevelamer carbonate (1500 mg/kg/day) or vehicle was started at the time point at which vascular calcification was present and continued for 3 weeks. Hyperphosphatemia and vascular calcification developed prior to treatment. A significant progression of aortic calcification in vehicle-treated rats with CKD was observed over the final 3-week period. Sevelamer treatment significantly reduced further progression of aortic calcification as compared to the vehicle control. No such an effect was seen for either PPi dose. Sevelamer but not PPi treatment resulted in an increase in both osteoblast and osteoid perimeter. Our study shows that sevelamer was able to reduce the progression of moderate to severe preexisting aortic calcification in a CKD rat model. Higher doses of PPi may be required to induce a similar reduction of severe established arterial calcification in this CKD model.
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium. ellen.neven@uantwerpen.be.
authors.forename: Ellen
authors.initials: E
authors.lastname: Neven
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Britt
authors.initials: B
authors.lastname: Opdebeeck
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: De Maré
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Rida
authors.initials: R
authors.lastname: Bashir-Dar
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Dams
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Rita
authors.initials: R
authors.lastname: Marynissen
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Behets
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Verhulst
authors.affiliation: BLR Bio, LLC, Kenosha, WI, USA.|Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Department of Medicine, Chicago Medical School, North Chicago, IL, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Riser
authors.affiliation: Laboratory of Pathophysiology, Department Biomedical Sciences, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Building T (Room 0.58), B-2610, Wilrijk, Belgium.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology; D011756:Diphosphates / Q000494:pharmacology*; D017886:Durapatite / Q000037:antagonists & inhibitors*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D000069603:Sevelamer / Q000494:pharmacology*; D061205:Vascular Calcification / Q000209:etiology / Q000473:pathology*
chemical_list: D002614:Chelating Agents; D011756:Diphosphates; C107241:diphosphoric acid; D017886:Durapatite; D000069603:Sevelamer
keywords: Bone; Chronic kidney disease; Preexisting vascular calcification; Pyrophosphate; Sevelamer