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Enhancing the hemocompatibility of dialysis membranes is crucial to reduce interactions between blood and the membrane, which can lead to blood activation. Inflammatory responses within the central nervous system may play a significant role in the development of mental disorders. This amplifies the heightened risk of psychological symptoms in dialysis patients, who experience increased inflammation due to ESRD. Additionally, depression is closely linked to inflammatory cytokines. This research aimed to: i) synthesize various new zwitterionic materials with different moieties and immobilized poly vinyl pyrrolidone (PVP) membranes; ii) assess the impact of these new membranes on inflammatory biomarkers and cytokines compared to the currently used membrane; and iii) correlate the levels of biomarkers with their potential impact on psychological symptoms.
Three different zwitterionic moiety membranes: sulfobetaine (PES-SB-ZW), phosphobetaine (PES-PH-ZW), and carboxybetaine (PES-CB-ZW), have been immobilized on polyether sulfone (PES). Additionally, we prepared polyvinyl pyrrolidone (PES-PVP) through UV-assisted photochemical synthesis. We recruited a cohort of five HD patients (n=5), and samples were collected before dialysis. Inflammatory biomarkers induced in uremic samples incubated with HD membranes for 1 hour were compared to samples incubated with PES for the same duration. Serum samples were prepared and subjected to Luminex assays, measuring C5a, IL-1α, IL-1β, IL-6, and C5b-9. The Shapiro-Wilk Normality Test was used for statistical analysis. Biomarker levels were correlated to the potential impact on psychological symptoms.
All modified membranes showed significantly lower C5b-9 levels, with reductions of -54.25% (P < 0.0001), -28.47% (P < 0.0001), -30.79% (P < 0.0001), and -59.26% (P < 0.0001) compared to the hospital membrane. Only PES-PVP exhibited lower C5a levels, with a reduction of -32.17% (P < 0.001), while other modified membranes showed an increase of up to 13.45% (P < 0.00245). Furthermore, after incubation of the membranes in collected uremic serum, the levels of IL-1β, IL-1α, and IL-6 for the bare PES membrane were 2.57 ± 0.20, 4.51 ± 1.01, and 13.34 ± 0.02 pg∙mL-1, respectively. However, PES-PH-ZW induced slightly higher IL-1β (+16.05%; P < 0.00245) and IL-1α (6.69%; P < 0.0001) levels and lower IL-6 (0.59%; p < 0.001). On the other hand, PES-CB-ZW resulted in notably lower IL-1β levels (-28.08%; P < 0.00245), minor increases in IL-1α (6.95%; P < 0.0001), and minor increases in IL-6 (3.5%; p < 0.001). In contrast, PES-SB-ZW led to a significant reduction in IL-1β (-43.81%; P < 0.002) and a decrease in IL-1α (-7.71%; P < 0.001), with a minor increase in IL-6 (5.32%; p < 0.001). The most favorable results were obtained with PES-PVP, which exhibited reductions of -8.57% (P < 0.001) for IL-1β and -6.18% (P < 0.001) for IL-6, while remaining the same as the neat membrane for IL-1α. Overall, higher cytokine levels contribute to the increase in C5a, possibly attributed to inherent free radicals.
The modification of dialysis membranes with PES-PVP resulted in a significant decrease in C5b-9 (-59.26%) and C5a (-32.17%). This has the potential to improve the quality of life for ESRD patients and may have implications for bipolar disorder. Other modifications showed improvements in C5b-9 and IL-1β, with the potential to enhance patient quality of life. However, they increased C5a or cytokines IL-1β and IL-6, warranting further investigation.