Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial

Am J Kidney Dis. 2012 Feb;59(2):177-85. doi: 10.1053/j.ajkd.2011.11.007. Epub 2011 Dec 2.


Background: Fibroblast growth factor 23 (FGF-23) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease (CKD). Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action, we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels.

Study design: Randomized prospective open-label trial.

Setting & participants: Patients with stage 4 CKD with hyperphosphatemia (n = 100).

Intervention: An 8-week intervention with sevelamer (n = 47) and calcium acetate (n = 53).

Outcomes: The primary study outcome was change in flow-mediated vasodilatation in the forearm. The secondary outcome was change in FGF-23 levels.

Results: Serum phosphate levels decreased in both treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001). Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer-treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs 6.0%). In a combined analysis, treatment-induced changes in flow-mediated vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23 levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%] for the calcium acetate group), as well as with C-reactive protein and fetuin A levels. These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors.

Limitations: Unblinded randomized controlled study that cannot establish mechanisms of effect.

Conclusions: In hyperphosphatemic patients with stage 4 CKD, treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation. These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population.

Trial registration: NCT01135615.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetates / pharmacology
  • Acetates / therapeutic use*
  • Adult
  • Calcium Compounds / pharmacology
  • Calcium Compounds / therapeutic use
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use
  • Chronic Disease
  • Comorbidity
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Forearm / blood supply*
  • Humans
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / epidemiology
  • Kidney Diseases / blood
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / epidemiology
  • Middle Aged
  • Phosphates / blood
  • Polyamines / pharmacology
  • Polyamines / therapeutic use*
  • Prospective Studies
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology*
  • Sevelamer
  • Severity of Illness Index
  • Treatment Outcome
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Acetates
  • Calcium Compounds
  • Chelating Agents
  • FGF23 protein, human
  • Phosphates
  • Polyamines
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Sevelamer
  • calcium acetate

Associated data