TY - JOUR
T1 - Inflammatory Markers and Incidence of Hospitalization with Infection in Chronic Kidney Disease the Chronic Renal Insufficiency Cohort Study
AU - Ishigami, Junichi
AU - Taliercio, Jonathan
AU - Feldman, Harold I.
AU - Srivastava, Anand
AU - Townsend, Raymond
AU - Cohen, Debbie L.
AU - Horwitz, Edward
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
N1 - Publisher Copyright:
© The Author(s) 2019
PY - 2021
Y1 - 2021
N2 - Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could 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 4 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 7.5 years), 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 (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. 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.
AB - Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could 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 4 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 7.5 years), 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 (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. 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.
KW - Chronic kidney disease
KW - Chronic renal insufficiency
KW - Infection
KW - Infectious disease
KW - Interleukin-1 receptor antagonist
KW - Interleukin-6
KW - Transforming growth factor-β
KW - Tumor necrosis factor-α
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U2 - 10.1093/AJE/KWZ246
DO - 10.1093/AJE/KWZ246
M3 - Article
C2 - 31673705
AN - SCOPUS:85086793257
SN - 0002-9262
VL - 189
SP - 433
EP - 444
JO - American journal of epidemiology
JF - American journal of epidemiology
IS - 5
ER -