Fibroblast Growth Factor 23, Urinary Phosphate, and Risk of Progression of CKD

Key Points High intact fibroblast growth hormone 23 levels, measured by automated chemiluminescent enzyme immunoassay, were associated with composite kidney outcomes in non–dialysis-dependent CKD. The association between intact fibroblast growth hormone 23 levels and outcomes was more pronounced in patients with low 24-hour urinary phosphate excretion. Fibroblast growth hormone 23 with 24-hour urinary phosphate excretion may assist in predicting the progression of CKD. Background Association between fibroblast growth hormone 23 (FGF23) levels and kidney outcomes and the effect of urinary phosphate excretion (UPE) on this association remain uncertain. This study aimed to investigate the association between FGF23 levels and kidney outcomes on the basis of UPE levels. Methods This observational study included 946 patients with non–dialysis-dependent CKD at a tertiary medical center in Japan. Intact FGF23 (iFGF23) levels were measured using an automated chemiluminescent enzyme immunoassay. The association between iFGF23 levels and composite kidney failure with replacement therapy and a 40% decline in eGFR was investigated using Cox regression analysis. A nonlinear relationship was investigated using restricted cubic spline analysis. Subgroup analyses on the basis of 24-hour UPE and fractional excretion of phosphate were also performed. Results The median eGFR level was 46 ml/min per 1.73 m 2 . During a median follow-up period of 27.2 months, 181 patients experienced composite kidney outcomes. Multivariable Cox regression analysis showed that the risk of composite kidney outcomes was higher in the highest FGF23 category of quartile 4 compared with that in a reference category of quartile 1, with a hazard ratio of 2.12 (95% confidence interval: 1.05 to 4.28). Restricted cubic spline analysis yielded consistent results. The association between high FGF23 levels and composite kidney outcomes was more pronounced in patients with low 24-hour UPE levels. However, fractional excretion of phosphate did not modify this association. Conclusions High iFGF23 levels are associated with composite kidney outcomes in patients with non–dialysis-dependent CKD. This association was more pronounced in those with low 24-hour UPE levels.