FGF23 and Left Ventricular Hypertrophy in Children with CKD

Clin J Am Soc Nephrol. 2018 Jan 6;13(1):45-52. doi: 10.2215/CJN.02110217. Epub 2017 Oct 12.

Abstract

Background and objectives: High plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD.

Design, setting, participants, & measurements: We performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH (LVMI ≥95th percentile), adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We also examined the relationship between FGF23 and LVH by eGFR level.

Results: Median age was 12 years (interquartile range, 8-15) and eGFR was 50 ml/min per 1.73 m2 (interquartile range, 38-64). Overall prevalence of LVH was 11%. After adjustment for demographics and body mass index, the odds of having LVH was higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants with FGF23 concentrations ≥170 RU/ml compared with those with FGF23<100 RU/ml, but this association was attenuated after full adjustment. Among participants with eGFR≥45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and 15.3% for those with FGF23 <100 RU/ml, 100-169 RU/ml, and ≥170 RU/ml, respectively (Ptrend=0.01). When eGFR was ≥45 ml/min per 1.73 m2, higher FGF23 concentrations were independently associated with LVH (fully adjusted odds ratio, 3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02 to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95% confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH.

Conclusions: Plasma FGF23 concentration ≥170 RU/ml is an independent predictor of LVH in children with eGFR≥45 ml/min per 1.73 m2.

Keywords: Body Mass Index; Confidence Intervals; EGFR protein, human; FGF23; Fibroblast Growth Factors; Hypertrophy, Left Ventricular; Logistic Models; Odds Ratio; Prevalence; Receptor, Epidermal Growth Factor; Renal Insufficiency, Chronic; adult; cardiovascular disease; child; children; chronic kidney disease; echocardiography; fibroblast growth factor 23; humans; left ventricular hypertrophy; risk factors.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / blood
  • Child
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate
  • Humans
  • Hypertrophy, Left Ventricular / blood*
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / epidemiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Kidney / physiopathology
  • Male
  • North America / epidemiology
  • Prevalence
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors
  • Severity of Illness Index
  • Up-Regulation
  • Ventricular Function, Left*
  • Ventricular Remodeling*

Substances

  • Biomarkers
  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23