Mononuclear leukocyte apoptosis and inflammatory markers in patients with chronic kidney disease

Am J Nephrol. 2012;36(6):531-6. doi: 10.1159/000345352. Epub 2012 Nov 29.

Abstract

Background/aim: Increased apoptosis along with enhanced inflammation has been reported in hemodialysis and pre-dialysis patients. However, there is limited information at which stage during the progression of chronic kidney disease (CKD) the balance between pro- and anti-apoptotic mechanisms is disturbed and inflammatory response is activated. The aim of this study was to investigate possible alterations in apoptotic and inflammatory markers during CKD (stages 1-4) progression and the probable interactions between them.

Methods: In a cross-sectional study, 152 steady-state CKD outpatients (83 males, 55%) with mean estimated glomerular filtration rate 46 (29-76) ml/min/1.73 m(2) were studied. Apoptosis was assessed in peripheral blood mononuclear cells by estimating Bcl-2 expression, annexin V-propidium iodine staining and serum soluble Fas (sFas) and Fas-ligand. Serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 and plasma levels of fibrinogen were measured as markers of inflammation.

Results: Bcl-2 expression was found to decrease significantly in both lymphocytes and monocytes from CKD stage 1 to 4. In contrast, the activity of sFas increased significantly and so did the levels of TNF-α and fibrinogen. The majority of these alterations occurred as soon as patients entered stage 3 of CKD. A multivariate regression analysis demonstrated that CKD remained a significant predictor of the aggregate of the assessed markers.

Conclusions: Apoptosis appeared to increase across CKD stages 1-4, and this was associated with increased proinflammatory activity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Fibrinogen / metabolism
  • Glomerular Filtration Rate
  • Humans
  • Inflammation / blood*
  • Interleukin-6 / blood
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / physiology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proto-Oncogene Proteins c-bcl-2 / blood
  • Renal Insufficiency, Chronic / blood*
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood
  • fas Receptor / blood

Substances

  • Biomarkers
  • FAS protein, human
  • Interleukin-6
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Fibrinogen
  • C-Reactive Protein