Article

Fibroblast growth factor 23 and Inflammation in CKD.

Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Clinical Journal of the American Society of Nephrology (impact factor: 5.23). 05/2012; 7(7):1155-62. DOI:10.2215/CJN.13281211
Source: PubMed

ABSTRACT 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.
The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-α, 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.
FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-α (r=0.4), and fibrinogen (r=0.3; P<0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (ln) transformed FGF23 was significantly associated with lnIL-6, lnCRP, lnTNF-α, and fibrinogen (P<0.001 for each). Each unit higher lnFGF23 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, 1.6-2.5]) 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).
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.

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  • Article: Risk of ESRD and All Cause Mortality in Type 2 Diabetes According to Circulating Levels of FGF-23 and TNFR1.
    Jung Eun Lee, Tomohito Gohda, William H Walker, Jan Skupien, Adam M Smiles, Rita R Holak, Jackson Jeong, Kevin P McDonnell, Andrzej S Krolewski, Monika A Niewczas
    [show abstract] [hide abstract]
    ABSTRACT: Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D). We studied 380 patients with T2D who were followed for 8-12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay. During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p<0.001). In the Cox multivariate model, circulating levels of FGF-23 remained a significant independent predictor of all-cause mortality unrelated to ESRD (HR 1.5, p<0.001). We demonstrated that the effect of circulating levels of FGF-23 on the risk of ESRD is accounted for by circulating levels of TNFR1. We confirmed that circulating levels of FGF-23 have an independent effect on all-cause mortality in T2D.
    PLoS ONE 01/2013; 8(3):e58007. · 4.09 Impact Factor
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Keywords

3879 participants
 
[95% confidence interval
 
adverse clinical outcomes
 
adverse outcomes
 
Ascending FGF23 quartiles
 
C-reactive protein
 
Chronic Renal Insufficiency Cohort
 
FGF23 correlated
 
fibroblast growth factor 23
 
greater odds
 
Higher FGF23 levels
 
highest 25th percentile
 
inflammation modifies
 
inflammatory markers IL-6
 
lowest FGF23 quartile [95% CI
 
multivariable-adjusted linear regression analyses
 
natural log
 
odds ratio [OR]
 
severe inflammation
 
unit higher lnFGF23