Plasma cytokines, glomerular filtration rate and adipose tissue cytokines gene expression in chronic kidney disease (CKD) patients

Nutr Metab Cardiovasc Dis. 2012 Nov;22(11):981-8. doi: 10.1016/j.numecd.2011.01.005. Epub 2011 Sep 8.

Abstract

Background and aim: Systemic inflammation is a hallmark of chronic kidney disease (CKD) and obesity represents a major risk factor for CKD. We investigated the relationship between plasma interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and the glomerular filtration rate (GFR) in 75 stage 2-5 CKD patients.

Methods and results: We studied the steady-state relationship between plasma and subcutaneous adipose tissue (SAT) gene expression of the same cytokines in 19 patients and in 17 well-matched healthy subjects (HS) and compared SAT gene expression of these cytokines and of two additional cytokines (IL-1β and IL-8) in CKD patients and in HS. Plasma IL-6 and TNF-α were higher in CKD patients than in HS (P < 0.001). IL-6 was similarly increased in patients with mild, moderate and severe CKD and largely independent of the GFR (r = -0.03, P = NS). TNF-α was inversely related to GFR, which was the first factor in rank (β = -0.37, P = 0.001) explaining the variability in TNF-α in CKD. SAT messenger RNA (mRNA) levels of IL-6, TNF-α, IL- β and IL-8 were similar in CKD patients and in HS. Plasma and SAT mRNA levels of IL-6 and TNF-α levels were largely unrelated.

Conclusions: Plasma IL-6 rises early in CKD and does not show any further increase at more severe stages of CKD, whereas TNF-α is inversely associated with the GFR indicating a substantial difference in the dynamics of the relationship between these cytokines and renal function. Cytokines are not overexpressed in SAT in these patients, and circulating IL-6 and TNF-α are dissociated from the corresponding mRNA levels in SAT, both in CKD patients and in HS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Gene Expression
  • Glomerular Filtration Rate
  • Humans
  • Interleukin-1beta / blood*
  • Interleukin-1beta / genetics
  • Interleukin-6 / blood*
  • Interleukin-6 / genetics
  • Interleukin-8 / blood*
  • Interleukin-8 / genetics
  • Linear Models
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / physiopathology
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha