Stefanovic Vladisav, Mitić-Zlatkovic Marina, Radivojevic Jasmina, Vlahovic Predrag
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Nis, Serbia.
Ren Fail. 2005;27(3):283-8.
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).
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.
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.
终末期肾病（ESKD）患者存在免疫缺陷状态，而血液透析（HD）会反常地加剧这种状态，并伴有T细胞激活迹象。尿毒症患者的B细胞也被激活，而促红细胞生成素治疗可能会改变HD患者的这种激活状态。在本研究中，我们对接受皮下注射重组人促红细胞生成素（rHu-EPO，15例患者，每周三次，每次2000 - 3000 U）或口服1-α-D3（14例患者，每周三次，每次2μg）治疗两个月的HD患者，研究了人重组促红细胞生成素（rHu-EPO）和1-α-D3治疗对淋巴细胞免疫调节酶、氨肽酶N（APN）以及5'-核苷酸酶活性的影响。
15例HD患者接受两个月的EPO治疗后，血红蛋白从6.51±0.18 g/dL升至9.69±0.14 g/dL。HD患者淋巴细胞的基础APN活性与健康对照者水平无显著差异。rHu-EPO治疗使未受刺激的淋巴细胞APN活性升高，显著高于治疗前水平（p<0.05）。14例HD患者接受两个月的脉冲口服1-α-D3治疗后，血细胞比容增加21%，血红蛋白从7.11±0.32 g/dL升至8.80±0.39 g/dL。脉冲口服1-α-D3后，未受刺激和经刀豆蛋白A（Con A）刺激的淋巴细胞APN活性较治疗前水平显著升高（分别为p<0.01和p<0.05）。HD患者淋巴细胞的基础、Con A刺激和佛波酯（PMA）刺激的5'-核苷酸酶活性显著高于健康对照者（p<0.05）。rHu-EPO或脉冲口服1-α-D3治疗两个月未改变这些患者淋巴细胞5'-核苷酸酶水平。
本研究表明，HD患者接受两个月的rHu-EPO或脉冲口服1-α-D3治疗可显著增加淋巴细胞APN活性，APN对裂解ESKD患者血液中积聚的肽和小蛋白很重要。HD患者淋巴细胞的胞外5'-核苷酸酶活性显著高于健康对照者，rHu-EPO或脉冲口服1-α-D3治疗两个月后未发生改变。我们推测氧化应激激活了HD患者淋巴细胞的5'-核苷酸酶并促使其产生腺苷。
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