Relationship between serum fibroblast growth factor-23 level and mortality in chronic hemodialysis patients

Fibroblast growth factor-23 (FGF23) is a phosphate-regulating hormone and is found to be markedly increased in patients with chronic kidney disease. The aim of the present study was to evaluate the relationship between serum FGF23 levels and mortality, including the impact of gender and cardiovascular disease (CVD), in a Japanese cohort of chronic hemodialysis (HD) patients.

Ninety-two maintenance dialysis patients (58 men; mean age 60.3 years) were included. Serum intact FGF23, calcium, phosphate, albumin, intact parathyroid hormone (PTH), and C-reactive protein were measured at baseline. CVD was defined as clinical symptoms and/or a history of CVD.

During a median follow-up time of 53.2 months, 24 patients (26 %) died. Serum FGF23 levels were positively correlated with serum levels of calcium (r = 0.5433, P < 0.0001), phosphate (r = 0.5048, P < 0.0001), calcium × phosphate product (r = 0.6801, P < 0.0001), and intact PTH (r = 0.2710, P = 0.0090) (r = 0.27, P < 0.0001). In Cox proportional hazard models, serum FGF23 level was not associated with increased mortality risk, neither in crude nor in multivariate-adjusted models. However, in a subgroup analysis of women with previous CVD, serum FGF23 level above median was associated with higher cardiovascular event risk in crude models (hazard ratio 9.52, 95 % confidence interval 1.56-86.11, P = 0.0129). Kaplan-Meier analysis stratifying for the presence of CVD demonstrated a significant higher mortality risk in patients with history of CVD and higher serum FGF23 levels (P < 0.0001).

Serum FGF23 level was not associated with increased mortality risk in this cohort of prevalent HD patients. These results suggest that the impact of FGF23 on mortality may be modified by gender and previous CVD and is blunted in the grade of hyperphosphatemia.