Fibroblast Growth Factor 23

Plasma

1 mL

0.3 mL (Note: This volume does not allow for repeat testing.)

Lavender-top (EDTA) tube

A morning 12-hour fasting sample is recommended but not required.

This test is used for measurement of Fibroblast Growth Factor 23 in plasma.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Enzyme-linked immunosorbent assay (ELISA).¹ This test is a second-generation C-terminal assay that measures both the intact FGF-23 and its C-terminal fragments.¹

Fibroblast growth factor 23 (FGF-23), a member of the fibroblast growth factor (FGF) family of proteins, is a phosphaturic hormone predominantly produced by bone osteocytes.^2-7 Plasma FGF-23 exerts its actions by binding to the FGF receptors on cell membranes. Effective FGF-23 binding to these cell surface receptors requires that the cell membrane also contain the transmembrane protein, Klotho.^2,8-11 FGF-23 inhibits phosphate reabsorption by suppressing Na/Pi cotransporter activity in the proximal convoluted tubule of the kidney. In addition, FGF-23 suppresses intestinal phosphate absorption by inhibiting 1-α-hydroxylase, the enzyme responsible for the conversion of calcifediol to calcitriol, the biologically active form of vitamin D.^2-4 FGF-23 also possibly inhibits parathyroid hormone (PTH) synthesis and secretion.^1-9 In healthy individuals, low levels of FGF-23 are detected in the circulation, and FGF-23 secretion rises with increased phosphorus intake and increased calcitriol levels.¹²

Elevated plasma FGF-23 activity has been associated with several hypophosphatemic diseases characterized by impaired renal phosphate reabsorption and rickets/osteomalacia.^5,6,9 Mutations in FGF-23 that render the protein resistant to proteolytic cleavage lead to increased FGF-23 activity and the renal phosphate loss found in autosomal-dominant hypophosphatemic rickets (ADHR). X-linked hypophosphatemic rickets (XLH)^5,6,9 and autosomal-recessive hypophosphatemic rickets (ARHR) are due to mutations in PHEX and dentin matrix protein 1, respectively. Both disorders are characterized by overproduction of FGF-23 by bone osteocytes. In tumor-induced osteomalacia (TIO), an acquired disorder of renal phosphate wasting associated with tumors, typically of mesenchymal origin; phosphatonins produced by the tumor promote renal phosphate wasting. FGF-23 is the most common phosphatonin found in patients with TIO.⁵ Patients with TIO share similar biochemical and skeletal phenotypes with patients who have ADHR, ARHR, and XLH.⁵

FGF-23 levels increase dramatically as renal function declines in chronic kidney disease (CKD) as the body attempts to overcome persistent phosphate retention.^2,4 FGF-23 elevation is thought to play a role in causing the disordered bone and mineral metabolism seen in CKD patients.^2,4 FGF-23 levels increase in parallel with the decline in renal function well before a significant increase in serum phosphate concentration or PTH occur.^2,4 Increased FGF-23 levels lead to reduced renal production of 1,25-dihydroxyvitamin D and to hypersecretion of parathyroid hormone.³ Prospective studies have demonstrated that elevated FGF-23 levels predict faster disease progression in CKD patients not on dialysis and increased mortality in patients undergoing maintenance hemodialysis and patients with renal transplants.^2,13 FGF-23 may predict future development of refractory hyperparathyroidism and cardiovascular events in CKD patients^3,14 and is thought to play a central role in the pathogenesis of post-transplant hypophosphatemia in kidney transplant recipients.³