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

Am J Epidemiol. 2020 May 5;189(5):433-444. doi: 10.1093/aje/kwz246.

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.

Keywords: chronic kidney disease; chronic renal insufficiency; infection; infectious disease; interleukin-1 receptor antagonist; interleukin-6; transforming growth factor-β; tumor necrosis factor-α.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

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