Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease

It is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC). This cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18 months–24 years, with various stages of CKD (eGFR = 11–214 mL/min). FGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) ( β = 0.660, p < 0.0001), log (PTH) ( β = 0.038, p = 0.37), and phosphate ( β = 0.222, p = 0.028) explained 69.1% of the variance of FGF-23. CysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD.