Year: 2010
Type: article
Abstract: Fibroblast growth factor 23 (FGF-23) is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through FGF receptors and the coreceptor Klotho. Besides reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, FGF-23 inhibits the renal 1α-hydroxylase and stimulates the 24-hydroxylase, and it appears to reduce parathyroid hormone (PTH) secretion in short-term studies. FGF-23 synthesis and secretion by osteocytes and osteoblasts is upregulated through 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and through an increased dietary phosphate intake. FGF-23 levels are elevated or inappropriately normal in patients with tumor-induced osteomalacia and several inherited hypophosphatemic disorders, but the most significant increases are found in patients with chronic kidney disease (CKD). During the early stages of CKD, increased FGF-23 production enhances urinary phosphate excretion and thus prevents the development of hyperphosphatemia, reduces the circulating levels of 1,25(OH)(2)D(3), and therefore contributes to the development of secondary hyperparathyroidism. In patients with end-stage renal disease (ESRD), FGF-23 levels can be extremely high and were shown to be predictors of bone mineralization, left ventricular hypertrophy, vascular calcification, and mortality. It remains to be determined, however, whether FGF-23 represents simply a sensitive biomarker of an abnormal phosphate homeostasis or has, independent of serum phosphate levels, potentially negative "off-target" effects. Nonetheless, reducing the production and/or the biologic activity of FGF-23 may be an important therapeutic goal for this patient population.
DOI: 10.1002/jbmr.170
Authors: Harald Jüppner, Myles Wolf, Isidro B. Salusky
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Role of FGF23 in Mineral Metabolism Across the Spectrum of Chronic Kidney Disease, Hormonal Control of Calcium Metabolism, G444342022, General Clinical Research Center, FGF23 and Cardiovascular Disease in CKD, Regulation of Bone Mineralization in Renal Osteodystrophy, Role of Parathyroid Hormone in Renal Osteodystrophy, G9000007873, G9000015409
OpenAlex ID: W2046983926