@article{c3d14b401a5f492dbe5005ba779af177,
title = "Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease",
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",
author = "{Munoz Mendoza}, Jair and Tamara Isakova and Xuan Cai and Bayes, {Liz Y.} and Christian Faul and Scialla, {Julia J.} and Lash, {James P.} and Jing Chen and Jiang He and Sankar Navaneethan and Lavinia Negrea and Rosas, {Sylvia E.} and Matthias Kretzler and Lisa Nessel and Dawei Xie and Anderson, {Amanda Hyre} and Raj, {Dominic S.} and Myles Wolf and Appel, {Lawrence J.} and Feldman, {Harold I.} and Go, {Alan S.} and Jiang He and Kusek, {John W.} and Lash, {James P.} and Akinlolu Ojo and Townsend, {Raymond R.}",
note = "Funding Information: Funding for the CRIC study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award National Institutes of Health/National Center for Advancing Translational Sciences UL1TR000003; Johns Hopkins University UL1 TR-000424; University of Maryland General Clinic Research Center M01 RR-16500; Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences component of the National Institutes of Health and National Institutes of Health roadmap for Medical Research; Michigan Institute for Clinical and Health Research UL1TR000433; University of Illinois at Chicago Clinical and Translational Science awards program UL1RR029879; Tulane University Translational Research in Hypertension and Renal Biology P30GM103337; and Kaiser Permanente National Institutes of Health/National Center for Research Resources University of California San Francisco?Clinical and Translational Science Institute UL1 RR-024131.",
year = "2017",
month = mar,
day = "1",
doi = "10.1016/j.kint.2016.10.021",
language = "English (US)",
volume = "91",
pages = "711--719",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "3",
}