Fibroblast Growth Factor 23 and Inflammation in CKD

Background and objectives Levels of fibroblast growth factor 23 (FGF23) and inflammatory markers are commonly elevated in CKD, and each is associated with adverse clinical outcomes. This study tested the hypothesis that FGF23 is independently associated with inflammation in CKD. Design, setting, participants, & measurements The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-alpha, and fibrinogen was assessed in a cross-sectional analysis of 3879 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study between June 2003 and September 2008. Results FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-alpha (r=0.4), and fibrinogen (r=0.3; P<0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (In) transformed FGF23 was significantly associated with InIL-6, InCRP, InTNF-alpha, and fibrinogen (P<0.001 for each). Each unit higher InFGF23 was associated with severe inflammation, defined as levels of all inflammatory markers in the highest 25th percentile, in univariate (odds ratio [OR], 2.4 [95% confidence interval (CI), 2.0-2.9]) and multivariable-adjusted (OR, 2.0 [95% CI, 1.6-2.51) logistic regression analyses. Ascending FGF23 quartiles were independently associated with severe inflammation (OR, 5.6 for the highest versus lowest FGF23 quartile [95% CI, 2.3-13.9]; P for trend < 0.001). Conclusions Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD. Clin J Am Soc Nephrol 7: 1155-1162, 2012. doi: 10.2215/CJN.13281211