Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.
BACKGROUND
Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure.


METHODS
Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date.


RESULTS
Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001).


CONCLUSIONS
Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.
Shigematsu
Takashi
T
Division of Nephrology, Tokyo-Jikeikai Medical School, Aoto Hospital, Tokyo, Japan.
Kazama
Junichiro James
JJ
Yamashita
Takeyoshi
T
Fukumoto
Seiji
S
Hosoya
Tatsuo
T
Gejyo
Fumitake
F
Fukagawa
Masafumi
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology*; D005921:Glomerulonephritis / Q000150:complications; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009399:Nephrons / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000652:urine
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium