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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.

SUBMITTER: Munoz Mendoza J

PROVIDER: S-EPMC5313324 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Munoz Mendoza Jair J Isakova Tamara T Cai Xuan X Bayes Liz Y LY Faul Christian C Scialla Julia J JJ Lash James P JP Chen Jing J He Jiang J Navaneethan Sankar S Negrea Lavinia L Rosas Sylvia E SE Kretzler Matthias M Nessel Lisa L Xie Dawei D Anderson Amanda Hyre AH Raj Dominic S DS Wolf Myles M

Kidney international 20161222 3

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 i ...[more]

PMID: 28017325

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Project description:Protein from plant, as opposed to animal, sources may be preferred in chronic kidney disease (CKD) because of the lower bioavailability of phosphate and lower nonvolatile acid load.Observational cross-sectional study.A total of 2,938 participants with CKD and information on their dietary intake at the baseline visit in the Chronic Renal Insufficiency Cohort Study.Percentage of total protein intake from plant sources (percent plant protein) was determined by scoring individual food items using the National Cancer Institute Diet History Questionnaire (DHQ).Metabolic parameters, including serum phosphate, bicarbonate (HCO?), potassium, and albumin, plasma fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH), and hemoglobin levels.We modeled the association between percent plant protein and metabolic parameters using linear regression. Models were adjusted for age, sex, race, diabetes status, body mass index, estimated glomerular filtration rate, income, smoking status, total energy intake, total protein intake, 24-hour urinary sodium concentration, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and use of diuretics.Higher percent plant protein was associated with lower FGF-23 (P = .05) and higher HCO? (P = .01) levels, but not with serum phosphate or parathyroid hormone concentrations (P = .9 and P = .5, respectively). Higher percent plant protein was not associated with higher serum potassium (P = .2), lower serum albumin (P = .2), or lower hemoglobin (P = .3) levels. The associations of percent plant protein with FGF-23 and HCO? levels did not differ by diabetes status, sex, race, CKD stage (2/3 vs. 4/5), or total protein intake (?0.8 g/kg/day vs. >0.8 g/kg/day; P-interaction >.10 for each).This is a cross-sectional study; determination of percent plant protein using the Diet History Questionnaire has not been validated.Consumption of a higher percentage of protein from plant sources may lower FGF-23 and raise HCO? levels in patients with CKD.

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

Publications

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

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