Inflammatory Markers and Incidence of Hospitalization With Infection in Chronic Kidney Disease.

Abstract

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.

• Authors: Junichi Ishigami, Jonathan Taliercio, Harold I Feldman, Anand Srivastava, Raymond Townsend, Debbie L Cohen, Edward Horwitz, Panduranga Rao, Jeanne Charleston, Jeffrey C Fink, Ana C Ricardo, James Sondheimer, Teresa K Chen, Myles Wolf, Tamara Isakova, Lawrence J Appel, Kunihiro Matsushita, CRIC Study Investigators
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 189 Issue 5 Pg. 433-444 (05 05 2020) ISSN: 1476-6256 [Electronic] United States
• PMID: 31673705 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Biomarkers
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-6
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Aged
• Biomarkers (blood)
• Disease Susceptibility
• Female
• Hospitalization (statistics & numerical data)
• Humans
• Incidence
• Infections (immunology)
• Inflammation (immunology)
• Interleukin 1 Receptor Antagonist Protein (blood)
• Interleukin-6 (blood)
• Male
• Middle Aged
• Prospective Studies
• Renal Insufficiency, Chronic (immunology)
• Transforming Growth Factor beta (blood)
• Tumor Necrosis Factor-alpha (blood)