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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 711-719 |
| Number of pages | 9 |
| Journal | Kidney International |
| Volume | 91 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2017 |
Fingerprint
Keywords
- CKD
- FGF23
- inflammation
- mortality
ASJC Scopus subject areas
- Medicine(all)
- Nephrology
Cite this
Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease. / Munoz Mendoza, Jair; Isakova, Tamara; Cai, Xuan; Bayes, Liz Y.; Faul, Christian H; Scialla, Julia J.; Lash, James P.; Chen, Jing; He, Jiang; Navaneethan, Sankar; Negrea, Lavinia; Rosas, Sylvia E.; Kretzler, Matthias; Nessel, Lisa; Xie, Dawei; Anderson, Amanda Hyre; Raj, Dominic S.; Wolf, Myles; Appel, Lawrence J.; Feldman, Harold I.; Go, Alan S.; He, Jiang; Kusek, John W.; Lash, James P.; Ojo, Akinlolu; Townsend, Raymond R.
In: Kidney International, Vol. 91, No. 3, 01.03.2017, p. 711-719.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease
AU - Munoz Mendoza, Jair
AU - Isakova, Tamara
AU - Cai, Xuan
AU - Bayes, Liz Y.
AU - Faul, Christian H
AU - Scialla, Julia J.
AU - Lash, James P.
AU - Chen, Jing
AU - He, Jiang
AU - Navaneethan, Sankar
AU - Negrea, Lavinia
AU - Rosas, Sylvia E.
AU - Kretzler, Matthias
AU - Nessel, Lisa
AU - Xie, Dawei
AU - Anderson, Amanda Hyre
AU - Raj, Dominic S.
AU - Wolf, Myles
AU - Appel, Lawrence J.
AU - Feldman, Harold I.
AU - Go, Alan S.
AU - He, Jiang
AU - Kusek, John W.
AU - Lash, James P.
AU - Ojo, Akinlolu
AU - Townsend, Raymond R.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - CKD
KW - FGF23
KW - inflammation
KW - mortality
UR - http://www.scopus.com/inward/record.url?scp=85010749584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85010749584&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2016.10.021
DO - 10.1016/j.kint.2016.10.021
M3 - Article
C2 - 28017325
AN - SCOPUS:85010749584
VL - 91
SP - 711
EP - 719
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 3
ER -