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Am J Epidemiol. 2019 Nov 1. pii: kwz246. doi: 10.1093/aje/kwz246. [Epub ahead of print]

Inflammatory Markers and Incidence of Hospitalization with Infection in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

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Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Nephrology and Hypertension, Cleveland Clinic Foundation, Cleveland, Ohio.
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Division of Nephrology, MetroHealth Medical Center, Cleveland, Ohio.
Division of Nephrology, University of Michigan, Ann Arbor, Michigan.
Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
Division of Nephrology, University of Illinois, Chicago, Illinois.
Division of Nephrology and Hypertension, Wayne State University School of Medicine, Detroit, Michigan.
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Division of Nephrology, Duke University School of Medicine, Durham, North Carolina.


Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation may impair immune response, it is unknown whether inflammatory markers are associated with infection risk in this clinical population. Using 2003-2013 data from the Chronic Renal Insufficiency Cohort Study (3,597 participants with CKD), we assessed the association of baseline plasma levels of four inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], interleukin-1 receptor antagonist [IL-1RA], and transforming growth factor-β [TGF-β]), with incident hospitalization with major infection (pneumonia, urinary tract infection, cellulitis and osteomyelitis, and bacteremia and sepsis). During follow-up (median 7.5years), 36% (n=1,290) had incident hospitalization with major infection. In multivariable Cox analyses with each inflammatory marker modeled as a restricted cubic spline, higher levels of IL-6 and TNF-α were monotonically associated with increased risk of hospitalization with major infection (HR at 95thvs.5thpercentile, 2.11 [95%CI,1.68,2.66] for IL-6 and 1.88 [1.51,2.33] for TNF-α), while corresponding associations for IL-1RA or TGF-β were non-significant. Thus, higher plasma levels of IL-6 and TNF-α, but not IL-1RA or TGF-β, were significantly associated with increased risk of hospitalization with major infection. Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD.


Chronic kidney disease; Chronic renal Insufficiency; Infection; Infectious disease; Interleukin-1 receptor antagonist; Interleukin-6; Transforming factor-β; Tumor necrosis factor-α


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