Apoptosis of peripheral CD4(+) T-lymphocytes in end-stage renal disease patients under hemodialysis and rhEPO therapies

Ren Fail. 2011;33(2):138-43. doi: 10.3109/0886022X.2011.553300.


End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Annexin A5 / analysis
  • Apoptosis*
  • Biomarkers / analysis
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / physiology
  • Case-Control Studies
  • Cross-Sectional Studies
  • Erythropoietin / adverse effects*
  • Female
  • Flow Cytometry
  • Humans
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / therapy
  • Lymphopenia / etiology*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Renal Dialysis / adverse effects*


  • Annexin A5
  • Biomarkers
  • Recombinant Proteins
  • Erythropoietin