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

Objectives: 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). Design and methods: 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). Results: 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) (beta=0.660, p < 0.0001), log (PTH) (beta=0.038, p=0.37), and phosphate (beta=0.222, p=0.028) explained 69.1% of the variance of FGF-23. Conclusions: 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. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.