Toxin Removal and Inflammatory State Modulation during Online Hemodiafiltration Using Two Different Dialyzers (TRIAD2 Study)

Abstract

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.

Assessment of the Influence of Asymmetric Triacetate Cellulose Membrane on the Rate of Removal of Middle Molecular Weight Uremic Toxins in Patients Treated with Postdilution Online Hemodiafiltration

“…During a single session of post-dilution OL-HDF, the mean decrease in serum IL-6 concentration was 2.90 ± 2.83 pg/mL, while the mean IL-6 reduction index was 43.75 ± 15.60%. These results are consistent with the results of other authors, who also showed that post-dilution OL-HDF with an asymmetric triacetate cellulose membrane reduces the concentration of pro-inflammatory mediators in serum [39], [40], [41].…”

“…The results of clinical studies show that postdilution OL-HDF with asymmetric triacetate cellulose membrane can be used as an alternative in patients with anamnestic data on hypersensitivity reactions to highpermeability polysulfone membranes, as well as in patients with increased risk of bleeding [41], [42], [43], [44]. The composition and structure of the asymmetric triacetate cellulose membrane enable the fulfillment of the criteria for high-volume post-dilution OL-HDF, while the modified cellulose fibers (absence of hydrophilizing agents) reduce the risk of allergic reactions.…”

“…The composition and structure of the asymmetric triacetate cellulose membrane enable the fulfillment of the criteria for high-volume post-dilution OL-HDF, while the modified cellulose fibers (absence of hydrophilizing agents) reduce the risk of allergic reactions. Membrane asymmetry reduces the degree of contact activation of platelets, so it may be an alternative to heparin-coated membranes [41], [42], [43], [44]. This membrane achieves a convective volume of more than 20 liters/ session, has good biocompatibility, reduces the concentration of pro-inflammatory mediators, and can be used in patients who develop allergic reactions to synthetic membranes [41], [42], [43], [44].…”

“…Membrane asymmetry reduces the degree of contact activation of platelets, so it may be an alternative to heparin-coated membranes [41], [42], [43], [44]. This membrane achieves a convective volume of more than 20 liters/ session, has good biocompatibility, reduces the concentration of pro-inflammatory mediators, and can be used in patients who develop allergic reactions to synthetic membranes [41], [42], [43], [44]. The incidence of hypersensitivity reactions to synthetic membranes is 2-5%, and according to some authors one episode per 12,000 dialysis sessions [45], [46], [47].…”

Albumin redox state of maintenance haemodialysis patients is positively altered after treatment

“…In conclusion, prospective cross over trials with different dialysis treatment modes and different dialyzer types like the one planned by Donati et al are needed to further evaluate to what extend dialyzer properties can reduce the level of oxidative stress [ 27 ].…”