FGF-23 levels in patients with AKI and risk of adverse outcomes

Abstract

Background and objectives: Fibroblast growth factor 23 plays an important role in regulating phosphate and vitamin D homeostasis. Elevated levels of fibroblast growth factor 23 are independently associated with mortality in patients with CKD and ESRD. Whether fibroblast growth factor 23 levels are elevated and associated with adverse outcomes in patients with AKI has not been studied.

Design, setting, participants, & measurements: This study had 30 participants with AKI, which was defined as an increase in serum creatinine ≥ 0.3 mg/dl or ≥ 50% from baseline, and 30 controls from the general hospital wards and intensive care units. Plasma levels of C-terminal fibroblast growth factor 23 and vitamin D metabolites were measured within 24 hours of AKI onset and 5 days later. The composite endpoint was death or need for renal replacement therapy.

Results: Enrollment fibroblast growth factor 23 levels were significantly higher among participants with AKI than controls (median [interquartile range]=1471 [224-2534] versus 263 [96-574] RU/ml, P=0.003). Enrollment fibroblast growth factor 23 correlated negatively with 25-hydroxyvitamin D (r=-0.43, P<0.001) and 1,25-dihydroxyvitamin D (r=-0.39, P=0.003) and positively with phosphate (r=0.32, P=0.02) and parathyroid hormone (r=0.37, P=0.005). Among participants with AKI, enrollment fibroblast growth factor 23 (but not other serum parameters) was significantly associated with the composite endpoint, even after adjusting for age and enrollment serum creatinine (11 events; adjusted odds ratio per 1 SD higher ln[fibroblast growth factor 23]=13.73, 95% confidence interval=1.75-107.50).

Conclusions: Among patients with AKI, fibroblast growth factor 23 levels are elevated and associated with greater risk of death or need for renal replacement therapy.

Figures

Figure 1.

Correlations between enrollment fibroblast growth factor 23 (FGF-23) and other serum parameters.

Figure 2.

Line plot of FGF-23 trend over time among those participants with AKI. (A) Participants who did not require renal replacement therapy (RRT). (B) Participants who were initiated on RRT. In A, solid lines represent individuals with interval improvement in creatinine (n=12); dotted lines represent individuals with interval worsening of creatinine (n=2).

Figure 3.

Progression to death/RRT based on tertiles of enrollment FGF-23 and creatinine among participants with AKI. *P=0.02 likelihood of progression to death/RRT among those participants in the highest compared with lowest FGF-23 tertiles.