title: FGF23: a mature renal and cardiovascular risk factor?
abstract: High FGF23 predicts renal function loss in chronic kidney disease (CKD) patients and graft failure in transplant patients. FGF23, parathyroid hormone and serum phosphate are all interrelated but among these CKD-MBD biomarkers only FGF23 is independently related with CKD progression. High FGF23 associates with endothelial dysfunction in CKD patients and in elderly individuals in the general population. Furthermore, independently of serum phosphate, high FGF23 associates with mortality and left ventricular hypertrophy in dialysis patients and with atherosclerosis in elderly individuals in the general population. FGF23 also predicts a high risk for death and cardiovascular events in predialysis CKD patients and in subjects with coronary artery disease. A recent trial in CKD patients showed that low phosphate intake associated with a phosphate binder produces a 35% decrease in plasma FGF23. Yet in this and in another trial testing several phosphate binders, FGF23 levels remained well beyond the upper limit of the normal range. Of note, in this latter study, calcification of the coronary arteries and abdominal aorta actually increased, rather than decreased, during treatment with these drugs in the face of evidence of negative phosphate balance and amelioration of hyperparathyroidism. Mechanistic studies are still needed before testing the hypothesis that FGF23 is implicated in a causal manner in cardiovascular and renal diseases. Given the modest effects of phosphate binders on serum FGF23 in CKD patients, pharmacologic interventions antagonizing the effects of this growth factor rather than phosphate-lowering interventions should be put in place to properly test this hypothesis in the clinical scenario in CKD.
authors.affiliation: Nephrology, Hypertension and Renal Transplantation Division and CNR-IBIM Clinical Epidemiology of Renal Diseases and Hypertension, Ospedali Riuniti, Reggio Calabria, Italy. carmine.zoccali@tin.it
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications* / Q000401:mortality; D018450:Disease Progression; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D010710:Phosphates / Q000097:blood; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications*; D012307:Risk Factors
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23