Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis

Bone. 2012 Jun;50(6):1266-74. doi: 10.1016/j.bone.2012.02.634. Epub 2012 Mar 6.


Purpose: Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD.

Methods: In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values.

Results: Mean estimated glomerular filtration rate (eGFR) was 35 mL/min/1.73 m(2). During a median duration of 4.4 years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27-2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P=0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91-1.48)). Complete case analyses yielded similar results.

Conclusions: Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation.

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Biomarkers / blood
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / complications
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / mortality
  • Cohort Studies
  • Female
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate
  • Humans
  • Japan / epidemiology
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Proportional Hazards Models
  • Prospective Studies
  • Renal Dialysis
  • Time Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood


  • Biomarkers
  • Parathyroid Hormone
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • 25-hydroxyvitamin D
  • Alkaline Phosphatase