Evaluation of oxidant-antioxidant balance in patients on maintenance haemodialysis: a comparative study of dialyzers membranes.

BACKGROUND: Haemodialysis (HD) exacerbates oxidative stress (OS). The polymethyl-methacrylate (PMMA)-BK-F membrane ameliorates OS and inflammation markers compared to polyacrylonitrile (PAN/AN69) and cellulose membranes. This may be due to the size of pore radius, high flux or other specific properties of PMMA membranes. AIM: To compare OS and inflammatory status in HD-treated end stage renal disease patients with membranes of different pore size radius and flux. METHODS: 47 patients of both sexes were studied. The HD membranes with which the patients were normally treated were changed to BK-P or B-3 membranes for 6 months. Intracellular and extracellular components of the oxidant-antioxidant balance (OAB), C-reactive protein (CRP), beta2-micro-globulin (beta2mu-globulin), albumin and transferrin were measured. RESULTS: A significant decrease in red cell membrane thiobarbituric acid reacting substances and an increase in cytosolic superoxide dismutase (SOD) and plasma total antioxidant substances were observed in all patients after 6 months of treatment with BK-P and B-3 membranes except SOD and CRP in patients previously dialysed with triacetate cellulose membranes. Albumin and transferrin remained unmodified. beta2mu-globulin significantly decreased after treatment with PMMA membranes. CONCLUSION: BK-P and B-3 HD membranes improved the OAB, beta2mu-globulin and CRP compared to PAN/AN69 and cellulose diacetate membranes.

Anemia associated with pegylated interferon-alpha2a and alpha2b therapy in hemodialysis patients.

AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.

BACKGROUND: Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life. AIM: To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD. METHODS: Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected. RESULTS: A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed. CONCLUSIONS: The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.

Leucopenia, hypoxia and complement activation in haemodialysis. Three unrelated phenomena.

Acute, transient leucopenia occurs in uraemic patients during the first minutes of haemodialysis, haemofiltration and ultrafiltration, and this leucopenia depends on the membrane used: maximal with cuprophan, less marked using cellulose acetate in haemofiltration and minimal with polyacrylonitrile. Complement activation was noted in all dialysis procedures except ultrafiltration. However, no correlation was found between the intensity of the complement activation and the degree of leucopenia. Significant hypoxia only appeared in haemodialysis using an acetate bath even with the polyacrylonitrile membrane. Sequential ultrafiltration-dialysis studies clearly demonstrate that leucopenia and hypoxia are unrelated effects of haemodialysis. Leucopenia depends on the membrane used and hypoxia may be related to the use of an acetate dialysate. In addition, the presence of dialysis fluid was necessary for membrane-induced complement activation suggesting an important influence of the dialysate on membrane biocompatibility.