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

: 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.