TNF and chronic kidney disease: Since studies in CKD patients have shown that higher serum FGF23 levels are associated with increased circulating concentrations of inflammatory cytokines, such as CRP, IL-6, IL-12, and tumor necrosis factor α (TNFα) (206–209), and that an elevation in these cytokines is a strong predictor of poor clinical outcome (210–213), the direct hepatic actions of FGF23/FGFR4 might serve as a novel pathomechanism that links CKD with systemic inflammation and contributes to morbidity and mortality (Figure 1).