FGF-23 and Cardio-Renal Interactions in Heart Failure

Abstract

Background Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone with a primary role in the regulation of phosphate homeostasis. Recently, FGF-23 was shown to be a strong predictor of cardiovascular outcomes, and animal models have reported multiple non-phosphaturic, or off-target, effects of FGF-23. Some of the negative cardio-renal actions reported in the literature are adverse left ventricular remodeling, induction of inflammation, renal/cardiac fibrosis, and direct effects on renal sodium retention. The aim of this current investigation was to further explore the association between FGF-23 with various parameters of cardio-renal dysfunction. Hypothesis FGF-23 will be associated with cardio-renal parameters such as inflammation, neurohormonal activation, diuretic responsiveness, and survival. Methods We analyzed plasma FGF-23 levels in 199 outpatient heart failure (HF) patients who underwent diuretic administration followed by timed urine collections. Diuretic response was defined as the sodium output per doubling of the diuretic dose. Results Higher levels of FGF-23 tended to correlate with serum phosphate (r=0.21, p=0.09) but were not correlated with serum calcium (p=0.37). There were stronger correlations between FGF-23 and several parameters of cardio-renal dysfunction including lower eGFR (r=-0.42, p 0.3 for both). Higher levels of FGF-23 predicted worse diuretic responsiveness (r=-0.47, p Conclusion In patients with HF, plasma levels of FGF-23 were associated with multiple metrics of cardio-renal dysfunction, including a strong independent association with diuretic responsiveness and mortality. Additional research is warranted to understand if FGF-23 is a marker or mediator of cardio-renal dysfunction and if interventions to lower FGF-23 levels can improve outcomes.