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). CONCLUSION: 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.
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). CONCLUSION: 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.
Authors: Victoria Shalhoub; Edward M Shatzen; Sabrina C Ward; James Davis; Jennitte Stevens; Vivian Bi; Lisa Renshaw; Nessa Hawkins; Wei Wang; Ching Chen; Mei-Mei Tsai; Russell C Cattley; Thomas J Wronski; Xuechen Xia; Xiaodong Li; Charles Henley; Michael Eschenberg; William G Richards Journal: J Clin Invest Date: 2012-06-25 Impact factor: 14.808