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 µg 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.