Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: A randomized clinical trial
American Journal of Kidney Diseases, cilt.59, sa.2, ss.177-185, 2012 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 59 Sayı: 2
- Basım Tarihi: 2012
- Doi Numarası: 10.1053/j.ajkd.2011.11.007
- Dergi Adı: American Journal of Kidney Diseases
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.177-185
- Anahtar Kelimeler: Fibroblast growth factor 23, endothelial dysfunction, inflammation, chronic kidney disease, sevelamer
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
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. © 2012 National Kidney Foundation, Inc.