Influence of Different Hemodialysis Membranes on Red Blood Cell Susceptibility to Oxidative Stress

Abstract

Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD. The addition of sodium azide enhanced this phenomenon. Both cellulose triacetate and polysulfone membranes did not significantly influence RBC susceptibility to oxidative stress. Neither the level of RBC reduced glutathione nor the RBC glutathione redox ratio changed significantly during HD with any of the membranes used. The RBC susceptibility to oxidative stress was influenced in different ways according to the dialysis membrane used, being increased only when using the more bioincompatible membrane Cuprophan, where neutrophil activation with increased free radical production is well documented. The alterations found in this study might contribute to the reduced RBC longevity of HD patients where a bioincompatible membrane is used.

Neutrophil Activation and Resistance to Recombinant Human Erythropoietin Therapy in Hemodialysis Patients

“…The interaction of blood with non-biological materials of the extracorporeal circuit during hemodialysis leads to the activation of several non-cellular and cellular systems, including polymorphonuclear leukocytes (PMN) [7, 8]. The activation of PMN may lead to degranulation, with release of several components, namely, cationic proteins and proteases and the production of oxygen metabolites.…”

Dialysis Membrane-Induced Oxidative Stress: Role of Heme Oxygenase-1

“…Canaud et al[ 29] suggested that patients on hemodialysis have a pro-oxidative state because of uremia, loss of antioxidant substances during dialysis, hemoincompatibility of the dialysis system and adjuvant therapy. Lucchi et al[ 30] reported increased malonaldehyde content of RBCs with the use of cuprophane membranes when compared with polysulfone and tricellulose acetate membranes. Zima et al[ 31] measured lipid peroxidation during hemodialysis.…”

Neutrophil Activation and Erythrocyte Membrane Protein Composition in Stage 5 Chronic Kidney Disease Patients

“…In stage 5 CKD patients, the erythrocytes are metabolically stressed by the unfavourable plasmatic environment, due to metabolite accumulation; by the high rate of haemoglobin autoxidation, due to the increase in haemoglobin turnover, a physiologic compensation mechanism triggered to compensate anaemia (Lucchi, 2000;Stoya, 2002). The erythrocytes will be further stressed during the haemodialysis procedure.…”

“…Erythrocytes are physically stressed during the haemodialysis process, and metabolically stressed by the unfavourable plasmatic environment, due to metabolite accumulation, and by the high rate of haemoglobin autoxidation, due to the increase in haemoglobin turnover, a physiologic compensation mechanism triggered in case of anaemia (Lucchi, 2000;Stoya, 2002). The erythrocytes are, therefore, continuously challenged to sustain haemoglobin in its reduced functional form, as well as to maintain the integrity and deformability of the membrane.…”

“…Spectrin is the major protein of the cytoskeleton, and, therefore, the primary cause of erythrocyte shape, integrity and deformability. It is linked to the lipid bilayer, by vertical protein interactions with the transmembrane proteins, band 3 and glicophorin A (Lucchi, 2000). In the vertical protein interaction of spectrin with band 3 there are also ankyrin (also known as band 2.1) and protein 4.2 involved.…”