Impact of anemia treatment with methoxy polyethylene glycol-epoetin beta on polymorphonuclear cells apoptosis in predialysis patients with chronic kidney disease

Pharmacol Rep. 2015 Oct;67(5):842-5. doi: 10.1016/j.pharep.2015.01.014. Epub 2015 Feb 7.

Abstract

Background: Some data in literature indicate increased apoptosis of polymorphonuclear cells (PMNs) in chronic kidney disease (CKD), what seems to be connected with anemia. Erythropoiesis-stimulating agents, used in anemia treatment in CKD may affect cells apoptosis. Aim of this study was to investigate impact of anemia treatment with methoxy polyethylene glycol-epoetin beta (CERA) on PMNs apoptosis in predialysis patients with CKD.

Methods: Percentage of early and late apoptotic PMNs was measured by flow cytometry based on annexin V and propidium iodide binding. CD90 (Fas), CD95L (FasL), CD16 and CD11b expression on PMNs were evaluated by flow cytometry after incubation with respective monoclonal antibody.

Results: Percentage of PMNs in early and late apoptosis in CKD patients before CERA treatment was significantly higher to control group, which was accompanied by significantly higher Fas and Fas-L expression and significantly lower expression of CD16. CERA treatment downregulated significantly percentage of early, apoptotic PMNs but percentage of late apoptotic cells did not change and was still significantly higher to control group. In all investigated groups we observed a significant negative correlation between hemoglobin concentration and percentage of apoptotic PMNs, as well as Fas and FasL expression and significant positive correlation between Hb and CD16 expression.

Conclusions: Our results indicate that PMNs apoptosis is increased in predialysis patients with CKD and anemia treatment with CERA may diminish readiness of PMNs to undergo apoptosis. This antiapoptotic impact of anemia treatment with CERA seems to concern early apoptotic PMNs before they undergo to late, irreversible stage of apoptosis.

Keywords: Apoptosis; Chronic kidney disease; Erythropoiesis-stimulating agents; Methoxy polyethylene glycol-epoetin beta (CERA); Polymorphonuclear cell.

MeSH terms

  • Adult
  • Anemia / drug therapy*
  • Apoptosis / drug effects*
  • Erythropoietin / therapeutic use*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Neutrophils / drug effects*
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Renal Dialysis
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / therapy

Substances

  • Recombinant Proteins
  • continuous erythropoietin receptor activator
  • epoetin beta
  • Erythropoietin
  • Polyethylene Glycols