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


CONCLUSIONS
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.
Stefanovic
V
V
Institute of Nephrology and Haemodialysis, Faculty of Medicine, 18000 Nis, Serbia. stefan@ni.ac.yu
Djordjevic
V
V
Ivic
M
M
Mitic-Zlatkovic
M
M
Vlahovic
P
P
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D048909:Diabetes Complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000628:therapy; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D002273:Carcinogens; D006887:Hydroxycholecalciferols; D011994:Recombinant Proteins; D003208:Concanavalin A; D004921:Erythropoietin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D013755:Tetradecanoylphorbol Acetate; C008088:alfacalcidol