title: Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients.
abstract: OBJECTIVE
  Fibroblast growth factor 23 (FGF23) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients. Sevelamer has been shown to reduce progression of vascular calcification. This study aimed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis (HD) patients.
  
  
  METHODS
  In the post-hoc analysis, we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH, hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. Twenty-three patients received sevelamer and 27 patients received calcium carbonate.
  
  
  RESULTS
  After 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.82 ± 0.78 to 1.65 ± 0.53 mmol/L, P = 0.000), lower FGF23 (from 2465.97 (2568.88) to 795.61 (1098.39), P = 0.000) and higher s-Klotho levels (from 189.35 (161.88) to 252.94 (517.80) pg/mL, P = 0.000). In calcium carbonate group, there were no significant changes of LDL-C and FGF23, but with a borderline significant increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P = 0.054). Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment (β = -0.277, P = 0.005), change of serum phosphate (β = 0.609, P = 0.000) and calcium levels (β = 0.635, P = 0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (β = 0.490, P = 0.019).
  
  
  CONCLUSIONS
  Maintenance HD patients had lower serum FGF23 levels, accompanied with significantly increased serum Klotho levels, after 48-week sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the change of serum phosphate and calcium levels. The serum Klotho increment was proportional to the phosphate-lowering power of the binders.
authors.affiliation: The Kidney Institute and Division of Nephrology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Lin
authors.forename: Hung-Hsiang
authors.initials: HH
authors.lastname: Liou
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Wu
authors.forename: Ching-Yuang
authors.initials: CY
authors.lastname: Lin
authors.forename: Chiu-Ching
authors.initials: CC
authors.lastname: Huang
mesh_terms: D002119:Calcium Carbonate / Q000627:therapeutic use; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000187:drug effects*; D005966:Glucuronidase / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000494:pharmacology* / Q000627:therapeutic use*; D011446:Prospective Studies; D006435:Renal Dialysis; D000069603:Sevelamer; D013997:Time Factors
chemical_list: C000717427:FGF23 protein, human; D011073:Polyamines; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; D005966:Glucuronidase; D000090265:Klotho Proteins; D002119:Calcium Carbonate
keywords: Klotho; chronic kidney disease; end-stage renal disease; fibroblast growth factor 23; haemodialysis; sevelamer