Vitamin E-Bonded Membranes Do Not Influence Markers of Oxidative Stress in Hemodialysis Patients with Homozygous Glutathione Transferase M1 Gene Deletion

Abstract

Background: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. Methods: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. Results: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. Conclusions: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

Influence of Dialysis Membranes on Clinical Outcomes: From History to Innovation

“…In a multicenter RCT conducted with two parallel groups of 94 patients on HD, theerythropoiesis-stimulating agent resistance index was decreased in the vitamin E-modified membrane group compared with the low-flux synthetic dialyzer group [52]. However, no significant change in the superoxide dismutase or C-reactive protein level or erythropoietin resistance index was observed in another RCT conducted with 80 patients with GSTM1-null genotypes on HD with vitamin E-modified membrane [53]. A systematic review and meta-analysis of 60 studies confirmed that vitamin E-modified membranes significantly decreased the concentrations of IL-6 (MW: 23,718 Da), thiobarbituric acidreactive substances (MW: 144 Da), and plasma and red blood cell malonylaldehyde (MW: 72 Da), but not those of other oxidizing agents, such as NOx (MW: 30-42 Da) in plasma [54].…”

New Strategies for the Reduction of Uremic Toxins: How Much More We Know

“…Improvements in dialysis membranes and techniques to remove medium-high molecular weight uremic toxins without a significant albumin loss were shown by expanded hemodialysis (HDx), a dialysis modality in which diffusion and convection are combined inside a hollow-fiber dialyzer containing a medium-cut-off (MCO) high-retention-onset membrane [9]. In contrast, vitamin E-bonded membranes showed no benefit in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking glutathione transferase M1 enzyme activity [10]. A paradigm shift from conventional dialysis therapies was represented by binding competitor-augmented hemodialysis.…”