Fibroblast Growth Factor-23—A Potential Uremic Toxin
AbstractFibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)2-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ–calcineurin–NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation. View Full-Text
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Kuczera, P.; Adamczak, M.; Wiecek, A. Fibroblast Growth Factor-23—A Potential Uremic Toxin. Toxins 2016, 8, 369.
Kuczera P, Adamczak M, Wiecek A. Fibroblast Growth Factor-23—A Potential Uremic Toxin. Toxins. 2016; 8(12):369.Chicago/Turabian Style
Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej. 2016. "Fibroblast Growth Factor-23—A Potential Uremic Toxin." Toxins 8, no. 12: 369.
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