Change in FGF23 concentration over time and its association with all-cause mortality in patients treated with haemodialysis or haemodiafiltration

Background: Previous studies in patients on haemodialysis (HD) have shown an association of fibroblast growth factor 23 (FGF23) with all-cause mortality. As of yet, the result of FGF23 lowering on mortality is unknown in this population.

Methods: FGF23 was measured in a subset of 404 patients from the Dutch CONvective TRansport STudy (CONTRAST study) [a randomized trial in prevalent dialysis patients comparing HD and haemodiafiltration (HDF) with clinical outcome] at baseline and Months 6 and 12. A substantial decline of FGF23 change over time was anticipated in patients randomized to HDF since HDF induces higher dialytic clearance of FGF23. The associations of both baseline FGF23 and 6-months change in FGF23 with all-cause mortality were analysed. In addition, the difference in FGF23 change between HD and HDF was explored. Furthermore, the role of dialysis modality in the association between FGF23 change and outcome was analysed.

Results: No association was observed between quartiles of baseline FGF23 and all-cause mortality. Over 6 months, FGF23 declined in patients on HDF, whereas FGF23 remained stable in patients on HD. A decrease in FGF23 was not associated with improved survival compared with a stable FGF23 concentration. However, increasing FGF23 was associated with a significantly higher mortality risk, both in crude and fully adjusted models [hazard ratio 2.01 (95% confidence interval 1.30-3.09)].

Conclusion: Whereas no association between a single value of FGF23 and all-cause mortality was found, increasing FGF23 concentrations did identify patients at risk for mortality. Since lowering FGF23 did not improve outcome, this study found no argument for therapeutically lowering FGF23.