The relationship between IL-10 levels and cardiovascular events in patients with CKD

Clin J Am Soc Nephrol. 2014 Jul;9(7):1207-16. doi: 10.2215/CJN.08660813. Epub 2014 May 1.

Abstract

Background and objectives: Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients.

Design, setting, participants, & measurements: Four hundred three patients with stages 1-5 CKD were followed for a mean of 38 (range=2-42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis.

Results: IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan-Meier survival curves showed that patients with IL-10 below the median value (<21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P<0.001).

Conclusions: IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.

Keywords: CKD; IL-10; cardiovascular disease; kidney disease.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Cross-Sectional Studies
  • Endothelium, Vascular / physiopathology
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-10 / blood*
  • Interleukin-6 / blood
  • Kaplan-Meier Estimate
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Regional Blood Flow
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors
  • Serum Amyloid P-Component / analysis
  • Time Factors
  • Up-Regulation
  • Vasodilation

Substances

  • Biomarkers
  • IL10 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Serum Amyloid P-Component
  • Interleukin-10
  • PTX3 protein
  • C-Reactive Protein