Fibroblast Growth Factor 23 and Mortality Among Prevalent Hemodialysis Patients in the Japan Dialysis Outcomes and Practice Patterns Study

Abstract

Introduction: Elevated fibroblast growth factor 23 (FGF23) levels have been strongly associated with mortality in the predialysis and incident hemodialysis populations, but few studies have examined this relationship in a large cohort of prevalent hemodialysis patients and in particular among persons with high dialysis vintage. To address this, we analyzed data from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS).

Methods: We included 1122 prevalent hemodialysis patients from the J-DOPPS phase 5 (2012-2015) who had FGF23 measurements. We evaluated the association of FGF23 levels with all-cause mortality and cardiovascular composite outcome using Cox regression adjusted for potential confounders.

Results: At study enrollment, median dialysis vintage was 5.8 years (interquartile range, 2.7-12.4 years) and median FGF23 level was 2113 pg/ml (interquartile range, 583-6880 pg/ml). During 3-year follow-up, 154 of the 1122 participants died. In adjusted analyses, higher FGF23 was associated with a greater hazard of death (hazard ratio per doubling of FGF23, 1.12; 95% confidence interval, 1.03-1.21); however, the association became weaker as the dialysis vintage increased and finally disappeared in the highest tertile (>9.4 years). Similar patterns of effect modification by dialysis vintage were observed for cardiovascular composite outcome and in time-dependent models.

Conclusion: Elevated FGF23 was associated with mortality and cardiovascular events in prevalent hemodialysis patients, but the association was attenuated at longer dialysis vintages. This novel finding suggests that long-term hemodialysis patients may be less susceptible to the detrimental effects of FGF23 or correlated biological processes, and additional studies are needed to gain understanding of these possibilities.

Keywords: FGF23; hemodialysis; kidney failure; mortality.

Graphical abstract

Figure 1

Association of fibroblast growth factor 23 (FGF23) with mortality using restricted cubic spline parameterization. Model 1 was adjusted for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, body mass index, albumin, and creatinine. Model 2 was adjusted for Model 1 covariates plus calcium, phosphorus, and intact parathyroid hormone. Model 3 was adjusted for Model 2 covariates plus active vitamin D treatment. HR, hazard ratio.