title: Cardiovascular effects of sevelamer in stage 3 CKD.
abstract: Serum phosphate independently predicts cardiovascular mortality in the general population and CKD, even when levels are in the normal range. Associations between serum phosphate, arterial stiffness, and left ventricular (LV) mass suggest a possible pathophysiological mechanism, potentially mediated by the phosphaturic hormone fibroblast growth factor-23 (FGF-23). To what extent the phosphate binder sevelamer modulates these effects is not well understood. In this single-center, randomized, double-blind, placebo-controlled trial, we enrolled 120 patients with stage 3 nondiabetic CKD. After a 4-week open-label run-in period, during which time all patients received sevelamer carbonate, we randomly assigned 109 patients to sevelamer (n=55) or placebo (n=54) for an additional 36 weeks. We assessed LV mass and systolic and diastolic function with cardiovascular magnetic resonance imaging and echocardiography, and we assessed arterial stiffness by carotid-femoral pulse wave velocity. The mean age was 55 years, and the mean eGFR was 50 ml/min per 1.73 m(2). After 40 weeks, we found no statistically significant differences between sevelamer and placebo with regard to LV mass, systolic and diastolic function, or pulse wave velocity. Only 56% of subjects took ≥ 80% of prescribed therapy; in this compliant subgroup, treatment with sevelamer associated with lower urinary phosphate excretion and serum FGF-23 but not serum phosphate, klotho, vitamin D, or cardiovascular-related outcomes of interest. In conclusion, this study does not provide evidence that sevelamer carbonate improves LV mass, LV function, or arterial stiffness in stage 3 nondiabetic CKD.
authors.affiliation: Schools of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chue
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.forename: William E
authors.initials: WE
authors.lastname: Moody
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
authors.forename: Nadezhda A
authors.initials: NA
authors.lastname: Wall
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D000069603:Sevelamer; D059289:Vascular Stiffness / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002614:Chelating Agents; C000717427:FGF23 protein, human; D011073:Polyamines; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer