Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease

Am J Physiol Heart Circ Physiol. 2014 Nov 15;307(10):H1504-11. doi: 10.1152/ajpheart.00331.2014. Epub 2014 Sep 12.

Abstract

Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min(-1)·1.73 m(-2)) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41-128 ml·min(-1)·1.73 m(-2)), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8-62.7) vs. 34.7 (interquartile range: 29.6-42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels (P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels (P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction (P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.

Keywords: chronic kidney disease; fibroblast growth factor 23; heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldosterone / blood
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Female
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate
  • Heart Failure / blood*
  • Heart Failure / diagnosis
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors
  • Severity of Illness Index
  • Stroke Volume
  • Systole
  • Up-Regulation
  • Ventricular Function, Left

Substances

  • Biomarkers
  • Aldosterone
  • Fibroblast Growth Factors
  • fibroblast growth factor 23