title: Mononuclear leukocyte apoptosis and inflammatory markers in patients with chronic kidney disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Nephrology of University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Dounousi
authors.forename: Elli
authors.initials: E
authors.lastname: Koliousi
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Papagianni
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Ioannou
authors.forename: Xanthi
authors.initials: X
authors.lastname: Zikou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Katopodis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Kelesidis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsakiris
authors.forename: Kostas C
authors.initials: KC
authors.lastname: Siamopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019014:fas Receptor / Q000097:blood
chemical_list: D015415:Biomarkers; C491901:FAS protein, human; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005340:Fibrinogen; D002097:C-Reactive Protein