Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients

Sci Rep. 2019 Dec 13;9(1):19103. doi: 10.1038/s41598-019-55592-y.


The major causes for increased morbidity and mortality among chronic kidney disease patients are cardiovascular diseases and infection. A causal link between an activated immune system and aggravated atherosclerosis has been postulated that skews the system towards inflammatory responses. Previously, we demonstrated a positive association of pro-inflammatory cytokines with monocytic Y-box binding protein-1 (YB-1) expression and vessel wall infiltration in hemodialysis patients. Here, we question whether the responsiveness and cytokine repertoire of monocytes is altered by pre-activation and how this correlates with survival. EDTA whole blood from hemodialysis patients (n = 45) and healthy controls (n = 34) was collected and leukocytes challenged with LPS. The distribution of monocyte subsets, YB-1acetyl content, and serum cytokine levels were determined. Compared to controls, dialysis patients have fewer classical (Mo1) and more intermediate (Mo2) and non-classical (Mo3) monocytes. In response to LPS, the Mo2 subset significantly increases (p < 0.001) in control subjects, but not in hemodialysis patients; increased CD86 expression indicates a positive response to LPS. Based on the changes within Mo2, subjects could be classified as responders or non-responders: 60% non-responders were seen in the dialysis cohort versus only 35% among healthy controls. YB-1 acetylation is higher in dialysis patients, independent of LPS stimulation. In this small cohort with 72 months follow-up period intracellular YB-1acetyl levels, IL-6, uPAR, and IP10 correlated with excess mortality in the dialysis cohort. Changes in YB-1 acetylation and serum cytokines may, at a given time point, possibly predict the long-term outcome and thus provide a legacy effect in hemodialysis patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / blood
  • Cytokines / metabolism
  • Diabetes Complications / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / blood*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Monocytes / cytology*
  • Monocytes / metabolism
  • Phenotype
  • Renal Dialysis*
  • Sepsis / blood*
  • Treatment Outcome
  • Y-Box-Binding Protein 1 / metabolism


  • Cytokines
  • Lipopolysaccharides
  • Y-Box-Binding Protein 1
  • YBX1 protein, human