FGF-23 Fibroblast Growth Factor 23
FGF-23 is produced in osteoblast precursor cells and is a potent regulator of phosphate and vitamin D metabolism.
Phosphate plays an essential role in the stability of skeletal bones and energy metabolism as well as in DNA synthesis and intracellular signal cascades.
FGF-23 inhibits in combination with cofactor Klotho phosphate reabsorption in renal proximal tubular cells via FGF-23 receptors (increased phosphate loss, reduced serum phosphate) and decreases calcitriol synthesis by suppressing alpha-1-hydroxylase.
FGF-23 in Osteology
FGF-23 is involved in a variety of diseases accompanied by hypophosphatemia caused by renal phosphate loss. Moreover, the clinical pictures show distinctly reduced calcitriol synthesis and osteomalacia or vitamin D resistant rickets.
- Tumor-induced osteomalacia / hypophosphatemia (TIO; paraneoplastic overexpression of FGF-23)
- Autosomal dominant hypophosphatemia rickets (ADHR; due to mutation in FGF-23 protein, FGF-23 cannot be inactivated by endopeptidases)
- X-linked hypophosphatemia (XHL, mutation in degrading enzyme (PHEX))
- Craniofacial dysplasia with hypophosphatemia (increased FGF-23 levels caused by mutation of FGF receptor 1)
- Fibrous dysplasia of bone (overproduction of FGF-23 due to mutation in G-protein subunit G5a/GNAS1)
FGF-23 in Nephrology
- Elevated FGF-23 values are seen in chronic renal insufficiency and correlate negatively with GFR.
- Increased serum FGF-23 levels may help maintain normophosphatemia in early chronic renal insufficiency until creatinine clearance is reduced to approximately 30 mL/min and hyperphosphatemia develops due to exhausted regulatory mechanisms and concurrently decreased calcitriol and sHPT.
- Monitoring of FGF-23 and serum phosphate in early chronic renal insufficiency allows, if necessary, to institute phosphate reduction therapy at an earlier stage.
- Creatinine levels within the normal range do not exclude disorders of phosphate metabolism.
- In the ArMoRR study published by Guitierrez et al. in August 2008, it was demonstrated that the FGF-23 level at the beginning of hemodialysis therapy may be seen as an independent risk marker. Patients showing FGF-23 levels within the highest range developed a 5.7fold higher risk of death within one year.
References
Guitierrez et al.: Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis. N Eng J Med 2008; 359: 584-92
Chi-yuan Hsu: FGF-23 and Outcomes Research – When Physiology meets Epidemiology. N Engl J Med 2008; 359 6
Andreas L. Serra et al.: Phosphatemic Effect of Cinacalcet in Kidney Transplant Recipients With Persistent Hyperparathyroidism. American Journal of Kidney Diseases 2008
