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Observational Study
. 2017 Mar;91(3):711-719.
doi: 10.1016/j.kint.2016.10.021. Epub 2016 Dec 22.

Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease

Jair Munoz Mendoza  1 , Tamara Isakova  2 , Xuan Cai  2 , Liz Y Bayes  3 , Christian Faul  1 , Julia J Scialla  4 , James P Lash  5 , Jing Chen  6 , Jiang He  6 , Sankar Navaneethan  7 , Lavinia Negrea  8 , Sylvia E Rosas  9 , Matthias Kretzler  10 , Lisa Nessel  11 , Dawei Xie  11 , Amanda Hyre Anderson  11 , Dominic S Raj  12 , Myles Wolf  13 ; CRIC Study Investigators
Collaborators, Affiliations
Observational Study

Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease

Jair Munoz Mendoza et al. Kidney Int. 2017 Mar.

Abstract

Inflammation is a consequence of chronic kidney disease (CKD) and is associated with adverse outcomes in many clinical settings. Inflammation stimulates production of fibroblast growth factor 23 (FGF23), high levels of which are independently associated with mortality in CKD. Few large-scale prospective studies have examined inflammation and mortality in patients with CKD, and none tested the interrelationships among inflammation, FGF23, and risk of death. Therefore, we conducted a prospective investigation of 3875 participants in the Chronic Renal Insufficiency Cohort (CRIC) study with CKD stages 2 to 4 to test the associations of baseline plasma interleukin-6, high-sensitivity C-reactive protein, and FGF23 levels with all-cause mortality, censoring at the onset of end-stage renal disease. During a median follow-up of 6.9 years, 550 participants died (20.5/1000 person-years) prior to end-stage renal disease. In separate multivariable-adjusted analyses, higher levels of interleukin-6 (hazard ratio per one standard deviation increase of natural log-transformed levels) 1.35 (95% confidence interval, 1.25-1.46), C-reactive protein 1.28 (1.16-1.40), and FGF23 1.45 (1.32-1.60) were each independently associated with increased risk of death. With further adjustment for FGF23, the risks of death associated with interleukin-6 and C-reactive protein were minimally attenuated. Compared to participants in the lowest quartiles of inflammation and FGF23, the multivariable-adjusted hazard ratio of death among those in the highest quartiles of both biomarkers was 4.38 (2.65-7.23) for interleukin-6 and FGF23, and 5.54 (3.04-10.09) for C-reactive protein and FGF23. Thus, elevated levels of interleukin-6, C-reactive protein, and FGF23 are independent risk factors for mortality in CKD.

Keywords: CKD; FGF23; inflammation; mortality.

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Figures

Figure 1
Figure 1. Kaplan–Meier analysis of cumulative incidence of mortality according to quartiles of inflammatory markers
(A) IL-6 (B) CRP
Figure 2
Figure 2. Additive effects of elevated levels of inflammatory markers and FGF23 on risk of mortality
(A) Crude mortality rates according to combined quartiles of IL-6 and FGF23. (B) Crude mortality rates according to a baseline quartiles of CRP and FGF23
Figure 2
Figure 2. Additive effects of elevated levels of inflammatory markers and FGF23 on risk of mortality
(A) Crude mortality rates according to combined quartiles of IL-6 and FGF23. (B) Crude mortality rates according to a baseline quartiles of CRP and FGF23
See this image and copyright information in PMC

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