title: Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure.
abstract: Elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease (CVD) in patients with chronic renal failure (CRF). The phosphate-binder sevelamer has been shown to decrease both phosphate and FGF23, but limited data indicate that sevelamer improves CRF-related CVD, such as diastolic dysfunction, left ventricular hypertrophy (LVH), and aortic stiffness. To gain additional information, we measured the effects of sevelamer on CVD in a murine model of CRF. Groups of CRF and sham-operated mice received regular chow or 3% sevelamer-HCl in the chow for 14 weeks, starting 6 weeks after the initiation of CRF or sham operation. After the first 8 weeks of sevelamer treatment, CRF mice had decreased serum phosphate levels and an improved aortic systolic expansion rate, pulse-wave velocity, and diastolic function, although LVH remained unchanged. Following an additional 6-week course of sevelamer, LVH had not progressed. The FGF23 serum level was not reduced by sevelamer until after 14 weeks of treatment. In multiple regression analysis, serum phosphate, but not FGF23, was independently correlated with LV diastolic function and mass. Thus, sevelamer first improved aortic stiffness and diastolic dysfunction and secondarily prevented LVH in mice with CRF. The phosphate-lowering, rather than FGF23-lowering, effect appears to be responsible for the observed cardiovascular improvement.
authors.affiliation: INSERM, Unit 1088 and Jules Verne University of Picardie, Amiens, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Maizel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Six
authors.forename: Sebastien
authors.initials: S
authors.lastname: Dupont
authors.forename: Edouard
authors.initials: E
authors.lastname: Secq
authors.forename: Benedicte
authors.initials: B
authors.lastname: Dehedin
authors.forename: Fellype C
authors.initials: FC
authors.lastname: Barreto
authors.forename: Joyce
authors.initials: J
authors.lastname: Benchitrit
authors.forename: Sabrina
authors.initials: S
authors.lastname: Poirot
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Jean C
authors.initials: JC
authors.lastname: Mazière
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drueke
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D000089703:Fibroblast Growth Factor-23; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology* / Q000627:therapeutic use*; D063177:Pulse Wave Analysis; D012044:Regression Analysis; D000069603:Sevelamer; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology
chemical_list: D002614:Chelating Agents; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D011073:Polyamines; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer