Comparison of Calcium Acetate and Sevelamer on Vascular Function and Fibroblast Growth Factor 23 in CKD Patients: A Randomized Clinical Trial

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. Am J Kidney Dis. 59(2):177-185. (C) 2012 by the National Kidney Foundation, Inc.