In patients with chronic kidney disease (CKD), adverse outcomes such as systemic inflammation and anemia are contributing pathologies which increase the risks for cardiovascular mortality. Amongst these complications, abnormalities in mineral metabolism and the metabolic milieu are associated with chronic inflammation and iron dysregulation, and fibroblast growth factor 23 (FGF23) is a risk factor in this context. FGF23 is a bone-derived hormone that is essential for regulating vitamin D and phosphate homeostasis. In the early stages of CKD, serum FGF23 levels rise 1000-fold above normal values in an attempt to maintain normal phosphate levels. Despite this compensatory action, clinical CKD studies have demonstrated powerful and dose-dependent associations between FGF23 levels and higher risks for mortality. A prospective pathomechanism coupling elevated serum FGF23 levels with CKD-associated anemia and cardiovascular injury is its strong association with chronic inflammation. In this review, we will examine the current experimental and clinical evidence regarding the role of FGF23 in renal physiology as well as in the pathophysiology of CKD with an emphasis on chronic inflammation and anemia.
Keywords: anemia; chronic kidney disease (CKD); erythropoietin (EPO); fibroblast growth factor 23 (FGF23); fibroblast growth factor receptor (FGFR); hepcidin; inflammation; klotho; phosphate.