Carozzi S, Nasini M G, Santoni O, Tirotta A, Sanna A
Nephrology, Dialysis and Transplantation Unit, St. Paul's Hospital, Savona, Italy.
ASAIO J. 1997 Sep-Oct;43(5):M535-8.
A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.
一定比例的血液透析（HD）患者对重组人促红细胞生成素（rHuEPO）耐药，这种现象在使用生物相容性膜（M）进行透析的患者以及腹膜透析患者中较少发生。作者评估了配对过滤透析（PFD）——一种基于使用血仿膜M与聚砜膜联合使用的透析技术——对rHuEPO耐药的HD患者红细胞生成的影响。研究了12例对rHuEPO长期治疗耐药的贫血HD患者（每周静脉注射3次，每次200.24 U/kg体重，共10.2个月）。患者平均使用铜仿膜M进行碳酸氢盐HD治疗46.9个月（A阶段），随后通过PFD治疗12个月（B阶段）。每月评估以下参数：1）血红蛋白和血细胞比容值；2）促红细胞生成素（EPO）的血清水平；3）白细胞介素（IL）-3、IL-6、IL-10、IL-1β、肿瘤坏死因子α（TNF-α）和干扰素γ（IFN-γ）的血清水平。在A阶段和B阶段结束时，患者接受骨髓活检以评估：1）骨髓红系爆式集落形成单位（BFU-E）和红系集落形成单位（CFU-E）的增殖能力；2）骨髓单个核细胞EPO受体（EPO-R）数量。在B阶段，血细胞比容和血红蛋白值逐渐升高，因此在第六个月内，rHuEPO剂量减至每周3次，每次80±15 U/kg体重。同时，血清IL-3、IL-6和IL-10水平升高，而血清IL-1β、TNF-α和IFN-γ水平降低。这伴随着BFU-E和CFU-E生长以及骨髓单个核细胞EPO-R数量的增加。在B阶段，透析后血清EPO水平与透析前值相比增加约30%，而在A阶段则降低约14%。在HD患者中，EPO耐药可能是由于rHuEPO被铜仿膜M吸附，或者是抑制红细胞生成的细胞因子如IL-1β、TNF-α和IFN-γ释放增加，以及刺激细胞因子如IL-3、IL-6和IL-10减少所致。使用PFD等生物相容性透析技术可逆转这些负面现象。
