title: Lymphocyte 5'-nucleotidase and aminopeptidase N activity in patients on maintenance hemodialysis treated with human recombinant erythropoietin and 1-alpha-D3.
abstract: BACKGROUND
  Patients with end-stage renal disease (ESKD) present an immunodeficiency state paradoxically exacerbated by hemodialysis (HD) and associated with signs of T-cell activation. B cells are also activated in uremia, and this activation could be altered by erythropoietin therapy in HD patients. In this study, the effects of human recombinant erythropoietin (rHu-EPO) and 1-alpha-D3 treatments on lymphocyte immunomodulatory enzymes, aminopeptidase N (APN), and 5'-nucleotidase activity in patients on HD were investigated in hemodialysis patients before and after two-month treatment with s.c. rHu-EPO (15 patients, 2000-3000 U three times weekly) or oral 1-alpha-D3 (14 patients, 2 microg three times weekly).
  
  
  RESULTS
  A two-month EPO treatment of 15 HD patients produced a rise in hemoglobin from 6.51 +/- 0.18 to 9.69 +/- 0.14 g/dL. Basal lymphocyte APN activity in HD patients was not significantly different from the level in healthy controls. Treatment of patients with rHu-EPO increased unstimulated lymphocyte APN activity to values significantly higher than those before treatment (p<0.05). A two-month pulse oral 1-alpha-D3 treatment of 14 HD patients increased hematocrit by 21% and raised hemoglobin from 7.11 +/- 0.32 to 8.80 +/- 0.39 g/dL. Unstimulated and Con A-stimulated lymphocyte APN activity after pulse oral 1-alpha-D3 was significantly increased (p<0.01 and p<0.05, respectively) from the pretreatment levels. In HD patients lymphocyte basal, Con A-, and PMA-stimulated 5'-nucleotidase activity was significantly higher (p<0.05) than it was in healthy controls. The two-month treatment with rHu-EPO or pulse oral 1-alpha D3 did not change the level of lymphocyte 5'-nucleotidase in these patients.
  
  
  CONCLUSIONS
  This study demonstrated that a two-month treatment of HD patients with rHu-EPO or pulse oral 1-alpha D3 significantly increases activity of lymphocyte APN, important for cleavage of peptides and small proteins, which accumulate in the blood of ESKD patients. In HD patients lymphocyte ecto-5'-nucleotidase activity was significantly higher than that in healthy controls and was not changed after a two-month treatment with rHu-EPO or pulse oral 1-alpha D3. We speculate that oxidative stress activates 5'-nucleotidase and production of adenosine by lymphocytes of HD patients.
authors.affiliation: Institute of Nephrology and Hemodialysis, Faculty of Medicine, Nis, Serbia. stefan@ni.ac.yu
authors.forename: Vladisav
authors.initials: V
authors.lastname: Stefanovic
authors.forename: Marina
authors.initials: M
authors.lastname: Mitić-Zlatkovic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Radivojevic
authors.forename: Predrag
authors.initials: P
authors.lastname: Vlahovic
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D014807:Vitamin D; C031271:1-alpha, 25-difluorovitamin D3; D015720:5'-Nucleotidase; D018826:CD13 Antigens