Lymphocyte PC-1 activity in patients on maintenance haemodialysis treated with human erythropoietin and 1-alpha-D3

Ann Clin Biochem. 2005 Jan;42(Pt 1):55-60. doi: 10.1258/0004563053026790.


Background: Plasma cell differentiation antigen 1 (PC-1) is an inhibitor of insulinreceptor tyrosine-kinase. PC-1 content is elevated in muscle and adipose tissue from insulin-resistant subjects and its elevation correlates with in vivo insulin resistance. It is known that insulin resistance in uraemia may be improved with erythropoietin (EPO) and vitamin D therapy. Therefore, in this study the effects of human recombinant EPO and 1-alpha-D3 treatments on lymphocyte PC-1 expression in patients with end-stage renal failure on haemodialysis (HD) were investigated.

Methods: Lymphocyte basal, concanavalin A (Con A), and phorbol-12-myristate13-acetate (PMA)-stimulated PC-1 activity were investigated in HD patients before and after a two-month treatment with subcutaneous EPO (15 patients, 2000-3000 U thrice weekly) or oral 1-alpha-D3 (14 patients, 2 mug thrice weekly). Twenty-nine patients (16 men and 13 women), aged 22-68 years (49+/-7 years), on HD from 13 to 112 months, and 30 healthy controls participated in the study. None was obese and all had normal fasting plasma glucose.

Results: A two-month EPO treatment produced a 41% haematocrit increase, with a rise in haemoglobin from 6.51+/-0.18 g/dL to 9.69+/-0.14 g/dL. Basal lymphocyte PC-1 activity in HD patients was found to be significantly increased (P<0.005) over the level in healthy controls. Treatment of patients with EPO decreased unstimulated lymphocyte PC-1 activity to values significantly lower than before the treatment (P<0.001). Lymphocyte Con A and PMA-stimulated PC-1 activity in patients on HD was found to be slightly increased over the level in healthy controls, but significantly reduced (P<0.005 and 0.05, respectively) after the EPO treatment. A two-month pulse oral 1-alpha-D3 treatment increased haematocrit by 21% and raised haemoglobin from 7.11+/-0.32 g/dL to 8.80+/-0.39 g/dL. This treatment normalized serum alkaline phosphatase activity and slightly reduced serum parathyroid hormone concentration. PC-1 in unstimulated and PMA-stimulated lymphocytes was unchanged, but significantly decreased (P<0.05) in Con A-stimulated lymphocytes after 1-alpha-D3 treatment. Fasting plasma glucose was not changed by the treatment.

Conclusion: An increased lymphocyte PC-1 activity over control was found in HD patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uraemic patients treated with EPO. Treatment with pulse oral 1-alpha-D3 had an effect only on PC-1 of Con A-transformed lymphocytes of haemodialysed patients and requires further investigation.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Administration, Oral
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Carcinogens / pharmacology
  • Concanavalin A / pharmacology
  • Diabetes Complications
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / therapy
  • Erythropoietin / therapeutic use*
  • Female
  • Humans
  • Hydroxycholecalciferols / therapeutic use*
  • Insulin Resistance*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / therapy*
  • Lymphocyte Activation / drug effects
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrophosphatases / metabolism*
  • Recombinant Proteins
  • Renal Dialysis*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Adjuvants, Immunologic
  • Blood Glucose
  • Carcinogens
  • Hydroxycholecalciferols
  • Recombinant Proteins
  • Concanavalin A
  • Erythropoietin
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases
  • Tetradecanoylphorbol Acetate
  • alfacalcidol