Abstract
Aims: The concentration of fibroblast growth factor 23 (FGF-23) is elevated in patients on dialysis. FGF receptors have been implicated in the pathogenesis of left ventricular (LV) hypertrophy. The objective of this study was to examine the associations between high plasma FGF-23 concentration and LV systolic dysfunction. Methods: We tested the hypothesis that high plasma FGF-23 concentration is associated with LV dysfunction in 110 chronic dialysis patients from the Homocysteine study who had paired echocardiograms performed for clinical indications. C-terminal FGF-23 concentrations were measured in stored plasma samples. Multivariate regression analyses were performed to evaluate the association of FGF-23 concentration with LV dysfunction. Results: Participants had a mean age of 60 ± 11 years. Median FGF-23 level and mean ejection fraction (EF) at baseline were 4,632 (1,384 – 14,997) RU/ml and 50 ± 13%, respectively. Median follow-up time was 1.9 years. Higher FGF-23 concentration was directly associated with decreases in EF during follow-up. After adjustment for demographics, baseline EF, hypertension, diabetes, cardiovascular disease, body mass index, systolic blood pressure, hemoglobin and markers of mineral metabolism, participants with FGF-23 in the highest tertile had an 8% decrease in EF compared to participants in the lowest tertile (β –8.0, 95% CI –15.5 to –0.53; p = 0.04). When FGF-23 was evaluated as a continuous variable, for every log10 increase in FGF-23, EF decreased during follow-up by 6.5% (β –6.5, 95% CI –11.3 to –1.73; p = 0.01). Conclusion: In conclusion, higher FGF-23 concentration is independently associated with LV systolic dysfunction in chronic dialysis patients.
Highlights
Estimates indicate that more than 20 million people have chronic kidney disease (CKD) in the United State [1]
We found that the association of fibroblast growth factor 23 (FGF-23) with left ventricular (LV) ejection fraction (EF) is the same independent of baseline LV mass index (LVMI) and Left ventricular hypertrophy (LVH) (p for interaction > 0.20 for all)
In our current prospective cohort of chronic dialysis patients, we found higher plasma FGF-23 concentrations to be directly associated with a decrease in LV EF during the study follow-up
Summary
Estimates indicate that more than 20 million people have chronic kidney disease (CKD) in the United State [1]. By the time patients reach end stage renal disease, FGF-23 concentrations are often 100 times above the normal range [6]. Elevated FGF-23 concentrations were found to be associated with death, cardiovascular events and kidney disease progression in patients with CKD [6, 7, 8, 9]. Elevated FGF-23 concentrations are independently associated with LVH in both the CKD and general population [12, 13, 14]. We conducted a longitudinal study to test the hypothesis that high plasma FGF-23 concentrations are associated with LV dysfunction independent of other factors that might influence systolic function in chronic dialysis patients utilizing the Homocysteine in Kidney and End Stage Renal Disease (HOST) Study [15] infrastructure
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