TY - JOUR
T1 - Fibroblast growth factor 23 and risk of hospitalization with infection in chronic kidney disease
T2 - The Chronic Renal Insufficiency Cohort (CRIC) study
AU - CRIC Study Investigators
AU - Ishigami, Junichi
AU - Taliercio, Jonathan T.
AU - Feldman, Harold I.
AU - Srivastava, Anand
AU - Townsend, Raymond R.
AU - Cohen, Debbie L.
AU - Horwitz, Edward J.
AU - Rao, Panduranga
AU - Charleston, Jeanne
AU - Fink, Jeffrey C.
AU - Ricardo, Ana C.
AU - Sondheimer, James
AU - Chen, Teresa K.
AU - Wolf, Myles
AU - Isakova, Tamara
AU - Appel, Lawrence J.
AU - Matsushita, Kunihiro
AU - Go, Alan S.
AU - He, Jiang
AU - Lash, James P.
AU - Rahman, Mahboob
N1 - Funding Information:
J. Ishigami was supported by National Heart, Lung, and Blood Institute grant T32HL007024. This research was also supported by National Institutes of Health (NIH)/ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01DK1100870 (to T. Isakova). Funding for the CRIC study was obtained under a cooperative agreement from NIDDKgrants 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 NIH/National Center for Advancing Translational Sciences Clinical and Translational Science Award UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland grant GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, National Center for Advancing Translational Sciences and NIH Roadmap for Medical Research grant UL1TR000439, Michigan Institute for Clinical and Health Research grant UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award UL1RR029879, Tulane University Center of Biomedical Research Excellence (COBRE) for Clinical and Translational Research in Cardiometabolic Diseases grant P20 GM109036, and Kaiser Permanente Washington Health Research Institute NIH/National Center for Research Resources (NCRR) University of California, San Francisco - Clinical & Translational Science Institute (UCSF-CTSI) grant UL1 RR-024131. H. Feldman reports grants from National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), during the conduct of the study. R. Townsend reports grants from NIH, during the conduct of the study. L. Appel reports grants from NIDDK, during the conduct of the study.
Funding Information:
Dr. Harold Feldman reports other from Kyowa Hakko Kirin Co, Ltd. and American Journal of Kidney Disease, outside the submitted work. Dr. Anand Srivastava reports personal fees from Horizon Pharma PLC, AstraZeneca, and CVS Caremark, outside the submitted work. Dr. Teresa K. Chen reports grants from NIH/NIDDK and Yale University, outside the submitted work. Dr. Myles Wolf reports personal fees from Amgen, DiaSorin, Akebia Therapeutics, AMAG Pharmaceuticals, Ardelyx, LUTIPOLD Pharmaceuticals, and Keryx Biopharmaceuticals, outside the submitted work. Dr. Tamara Isakova reports personal fees from Kyowa Kirin and LifeSci Capital, outside the submitted work. Dr. Kunihiro Matsushita reports grants from NIH: research funding, personal fees from Akebia, and grants and personal fees from Kyowa Kirin, outside the submitted work.
Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology
PY - 2020/8
Y1 - 2020/8
N2 - Background Risk of infectious disease is increased among individuals with CKD. Fibroblast growth factor 23 (FGF23) is often elevated in CKD, and may impair immune function directly or indirectly through proinflammatory and vitamin D–suppressing pathways. Whether FGF23 is associated with risk of infection has not been evaluated in a CKD population. Methods In 3655 participants of the Chronic Renal Insufficiency Cohort study, we evaluated the association of baseline plasma levels of C-terminal FGF23 with time to first hospitalization with major infection, defined by hospital discharge with a diagnosis code for urinary tract infection, pneumonia, cellulitis/osteomyelitis, or bacteremia/septicemia. Multivariable Cox models were used to estimate hazard ratios (HRs) and adjust for confounding. Results During a median follow-up of 6.5 years, 1051 individuals (29%) were hospitalized with major infection. Multivariable Cox analysis indicated a graded increase in the risk of infection with higher levels of FGF23 (HR, 1.51; 95% CI, 1.23 to 1.85 with the highest quartile [$235.9 RU/ml] versus lowest quartile [,95.3 RU/ml]; HR, 1.26; 95% CI, 1.18 to 1.35 per SD increment in log FGF23). The association was consistent across infection subtypes and demographic and clinical subgroups, and remained significant after additional adjustment for biomarkers of inflammation (IL-6, TNF-a, high-sensitivity C-reactive protein, fibrinogen, and albumin), and bone mineral metabolism (25-hydroxyvitamin D, phosphorus, calcium, and parathyroid hormone). The association was consistent across infection subtypes of urinary tract infection (482 cases), cellulitis/osteomyelitis (422 cases), pneumonia (399 cases), and bacteremia/septicemia (280 cases). Conclusions Among individuals with CKD, higher FGF23 levels were independently and monotonically associated with an increased risk of hospitalization with infection.
AB - Background Risk of infectious disease is increased among individuals with CKD. Fibroblast growth factor 23 (FGF23) is often elevated in CKD, and may impair immune function directly or indirectly through proinflammatory and vitamin D–suppressing pathways. Whether FGF23 is associated with risk of infection has not been evaluated in a CKD population. Methods In 3655 participants of the Chronic Renal Insufficiency Cohort study, we evaluated the association of baseline plasma levels of C-terminal FGF23 with time to first hospitalization with major infection, defined by hospital discharge with a diagnosis code for urinary tract infection, pneumonia, cellulitis/osteomyelitis, or bacteremia/septicemia. Multivariable Cox models were used to estimate hazard ratios (HRs) and adjust for confounding. Results During a median follow-up of 6.5 years, 1051 individuals (29%) were hospitalized with major infection. Multivariable Cox analysis indicated a graded increase in the risk of infection with higher levels of FGF23 (HR, 1.51; 95% CI, 1.23 to 1.85 with the highest quartile [$235.9 RU/ml] versus lowest quartile [,95.3 RU/ml]; HR, 1.26; 95% CI, 1.18 to 1.35 per SD increment in log FGF23). The association was consistent across infection subtypes and demographic and clinical subgroups, and remained significant after additional adjustment for biomarkers of inflammation (IL-6, TNF-a, high-sensitivity C-reactive protein, fibrinogen, and albumin), and bone mineral metabolism (25-hydroxyvitamin D, phosphorus, calcium, and parathyroid hormone). The association was consistent across infection subtypes of urinary tract infection (482 cases), cellulitis/osteomyelitis (422 cases), pneumonia (399 cases), and bacteremia/septicemia (280 cases). Conclusions Among individuals with CKD, higher FGF23 levels were independently and monotonically associated with an increased risk of hospitalization with infection.
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U2 - 10.1681/ASN.2019101106
DO - 10.1681/ASN.2019101106
M3 - Article
C2 - 32576601
AN - SCOPUS:85089127240
VL - 31
SP - 1836
EP - 1846
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 8
ER -