Gutiérrez OM et al. (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359: 584–592

In patients with kidney disease, the level of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) is increased in order to maintain phosphate balance. Hyperphosphatemia is a known risk factor for death in this population; however, the relationship between FGF-23 level and mortality is unknown. By use of data from a prospective cohort study of 10,044 US patients who initiated hemodialysis in 2004–2005, Gutiérrez et al. attempted to clarify this issue.

Patients in the highest quartile of serum phosphate level (>1.8 mmol/l) had a 1.2-fold greater risk of death than those in the quartile with normal serum phosphate levels (1.1–1.5 mmol/l). A case–control study of 200 participants who survived the first year of dialysis and 200 who did not showed that the median plasma level of C-terminal FGF-23 fragments (cFGF-23) was lower among survivors than among nonsurvivors (1,406 U/ml vs 2,260 U/ml; P <0.001). This trend persisted when each quartile of serum phosphate level was examined separately, apart from the highest quartile, in which the difference was not significant. After adjustment for case-mix factors and laboratory variables, each unit increase in the natural log-transformed cFGF-23 level was associated with a 1.8-fold increase in mortality risk. Patients in the highest quartile of cFGF-23 had a 5.7-fold greater risk of death than those in the lowest quartile.

Increased FGF-23 levels seem to predict mortality among incident hemodialysis patients independently of serum phosphate level and might provide a means of identifying patients with normal serum phosphate levels who could benefit from phosphate-lowering treatment.