Curr Opin Nephrol Hypertens 2016[Jul]; 25 (4): 333-42 PMID27219044show ga
Purpose of the review: This review examines therole of FGF-23 in mineral metabolism, innate immunity and adverse cardiovascular outcomes. Recent findings: FGF-23, produced by osteocytes in bone, activates FGFR/?-Klotho complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of Vitamin D on innate immunity and cardiovascular responses. FGF-23 is ectopically expressed along with ?-Klotho in activated macrophages, creating a pro-inflammatory paracrine signaling pathway that counters the anti-inflammatory actions of vitamin D. FGF-23 also inhibits ACE2 expression and increases sodium reabsorption in the kidney, leading to hypertension and left ventricular hypertrophy. Finally, FGF-23 is purported to cause adverse cardiac and impair neutrophil responses through activation of FGFRs in the absence of ?-Klotho. While secreted forms of ?-Klotho have FGF-23- independent effects, the possibility of ?-Klotho-independent effects of FGF-23 is controversial and requires additional experimental validation. Summary: FGF-23 participates in a bone-kidney axis regulating mineral homeostasis, proinflammatory paracrine macrophage signaling pathways, and in a bone-cardio-renal axis regulating hemodynamics that counteract the effects of Vitamin D.