Extrarenal effects of FGF23.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular mortality, infections, and impaired cognitive function. It is characterized by excessively increased levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and a deficiency of its co-receptor Klotho. Despite the important physiological effect of FGF23 in maintaining phosphate homeostasis, there is increasing evidence that higher FGF23 levels are a risk factor for mortality and cardiovascular disease. FGF23 directly induces left ventricular hypertrophy via activation of the FGF receptor 4/calcineurin/nuclear factor of activated T cells signaling pathway. By contrast, the impact of FGF23 on endothelial function and the development of atherosclerosis are poorly understood. The results of recent experimental studies indicate that FGF23 directly impacts on hippocampal neurons and may thereby impair learning and memory function in CKD patients. Finally, it has been shown that FGF23 interferes with the immune system by directly acting on polymorphonuclear leukocytes and macrophages. In this review, we discuss recent data from clinical and experimental studies on the extrarenal effects of FGF23 with respect to the cardiovascular, central nervous, and immune systems.