High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients

Abstract

Background: Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival.

Methods: All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles.

Results: The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality.

Conclusion: This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.