Abstract
BACKGROUND: Fibroblast growth factor-23 (FGF-23) is associated with mortality in dialysis patients, and concentrations are elevated in moderate chronic kidney disease (CKD). The threshold of CKD or albuminuria at which FGF-23 begins to change is unknown. METHODS: In 792 outpatients with stable cardiovascular disease (CVD) and normal kidney function to moderate CKD, we evaluate the associations of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) with plasma FGF-23 concentrations. RESULTS: Compared to participants with eGFR >or=90 ml/min/1.73 m(2), mean FGF-23 concentrations were 7.8 RU/ml higher (4.3-11.5, P = 0.01) in those with eGFR 60-89 ml/min/1.73 m(2) in models adjusted for age, sex, race, ACR, blood pressure, diabetes and body mass index. More advanced decrements in eGFR were associated with much higher FGF-23 concentrations. In spline analysis, the slope of change in FGF-23 concentration was evident at eGFR <90 ml/min/1.73 m(2). Compared to participants with ACR <30 mg/g, mean FGF-23 concentrations were 18.4 RU/ml higher (9.3-29.2, P < 0.001) in those with ACR 30-299 mg/g in models adjusted for identical covariates plus eGFR and much higher in individuals with ACR >or=300 mg/g. Spline analysis demonstrated a linear relationship of ACR with FGF-23, independent of eGFR, even among persons with ACR <30 mg/g. CONCLUSION: Modest decrements in eGFR or elevations in albuminuria are each independently associated with higher FGF-23 concentrations in outpatients with stable CVD.