J Bone Metab.  2018 Aug;25(3):153-159. 10.11005/jbm.2018.25.3.153.

Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer

• Ghorbanihaghjo A
• Argani H
• Golmohamadi Z
• Rashtchizadeh N
• Abbasi MM
• Bargahi N
• Vatankhah
• Sanajou D

• KMID: 2419842
• DOI: http://doi.org/10.11005/jbm.2018.25.3.153

Abstract

BACKGROUND
High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD.
METHODS
CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods.
RESULTS
Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P < 0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P < 0.01).
CONCLUSIONS
Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.

Keyword

Chronic; Phosphates; Renal insufficiency; Sevelamer

MeSH Terms

Adenine
Animals
Diet
Enzyme-Linked Immunosorbent Assay
Fibroblast Growth Factors*
Fibroblasts*
Humans
Models, Animal
Mortality
Osteocytes
Phosphates
Rats
Renal Insufficiency
Renal Insufficiency, Chronic
Risk Factors
Sevelamer*
Spectrophotometry
Adenine
Fibroblast Growth Factors
Phosphates
Sevelamer

Figure

• 

  Fig. 1 The experimental design. From 0 week to 4 weeks, adenine diet was administered for the four groups (CKD control group, 1%, 2%, or 3 % sevelamer administered groups). At day 28, adenine diet was stopped and after that normal diet was used. At day 28 the administration of sevelamer was started and sevelamer was administered at 1%, 2%, or 3 % mixture diet for 4 weeks. Next group included normal rats, fed 3% sevelamer. CKD, chronic kidney disease.

• 

  Fig. 2 Correlation between serum FGF-23 and phosphate in chronic kidney disease and sevelamer treated groups. FGF-23, fibroblast growth factor-23.

• 

  Fig. 3 Relation between FGF-23 and Ca×P product in chronic kidney disease and sevelamer treat groups. FGF-23, fibroblast growth factor-23; Ca, calcium; P, phosphorus.

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