Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKD

Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1930-1940. doi: 10.2215/CJN.03030317. Epub 2017 Oct 26.

Abstract

Background and objectives: Epidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4.

Design, setting, participants, & measurements: Patients with CKD, eGFR between 45 and 15 ml/min per 1.73 m2, fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast growth factor 23 >80 relative units/ml were included in our double-blind, placebo-controlled, randomized multicenter study. All patients received 100,000 IU cholecalciferol at time of randomization. Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters, including serum C-terminal fibroblast growth factor 23, intact fibroblast growth factor 23, and α-klotho, were evaluated at baseline and 12 weeks after inclusion.

Results: Of 96 screened patients, 78 (mean±SD age: 63±13 years old; 70% men; mean eGFR: 27±9 ml/min per 1.73 m2) met the inclusion criteria. At baseline, mean eGFR was 27±9 ml/min per 1.73 m2, mean serum phosphate level was 3.8±0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of treatment, urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group. The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels: the median (interquartile range) change was 38 (-13-114) relative units/ml in the placebo group and 37 (-1-101) relative units/ml in the sevelamer group (P=0.77). There was no significant difference in serum intact fibroblast growth factor 23, α-klotho, or phosphate levels changes between the two groups. Serum total and LDL cholesterol levels fell significantly in the sevelamer group.

Conclusions: In our double-blind, placebo-controlled, randomized study performed in normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or α-klotho levels.

Keywords: Cholecalciferol; Cholesterol, LDL; Double-Blind Method; Epidemiologic Studies; FGF23; Fasting; Fibroblast Growth Factors; Hypophosphatemia, Familial; KLOTHO; Phosphates; Phosphorus; Random Allocation; Renal Insufficiency, Chronic; chronic kidney disease; creatinine; fibroblast; fibroblast growth factor 23; glomerular filtration rate; mineral metabolism; phosphate binders; randomized controlled trials; sevelamer.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Chelating Agents / adverse effects
  • Chelating Agents / pharmacology*
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Female
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate
  • Glucuronidase / blood*
  • Humans
  • Male
  • Middle Aged
  • Phosphorus / blood
  • Phosphorus / urine*
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / drug therapy*
  • Sevelamer / adverse effects
  • Sevelamer / pharmacology*

Substances

  • Chelating Agents
  • Cholesterol, LDL
  • Phosphorus
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Sevelamer
  • Glucuronidase
  • klotho protein