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: Vladisav Stefanovic, Marina Mitić-Zlatkovic, Jasmina Radivojevic, Predrag Vlahovic
• Journal: Renal failure (Ren Fail) Vol. 27 Issue 3 Pg. 283-8 ( 2005) ISSN: 0886-022X [Print] England
• PMID: 15957544 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Hemoglobins
• Recombinant Proteins
• Erythropoietin
• Vitamin D
• 1-alpha, 25-difluorovitamin D3
• 5'-Nucleotidase
• CD13 Antigens

Topics

• 5'-Nucleotidase (metabolism)
• Administration, Oral
• Adult
• Aged
• Anemia (blood, drug therapy, etiology)
• Biomarkers (metabolism)
• CD13 Antigens (metabolism)
• Cells, Cultured
• Drug Therapy, Combination
• Erythropoietin (administration & dosage, therapeutic use)
• Female
• Follow-Up Studies
• Hemoglobins (metabolism)
• Humans
• Kidney Failure, Chronic (blood, complications, therapy)
• Lymphocytes (cytology, enzymology)
• Male
• Middle Aged
• Recombinant Proteins
• Treatment Outcome
• Vitamin D (administration & dosage, analogs & derivatives, therapeutic use)