Comparison of the Removal of Uremic Toxins With Medium Cut-off and Super High-flux Vitamin E-coated Dialyzers

Overview

End-stage renal disease (ESRD) induces an accumulation of uremic toxins responsible for increased morbidity and mortality. These toxins cover a wide range of molecules, classified according to their molecular weight as small-size (\< 500 Da), middle-size (500 Da-60 kDa), and protein-bound toxins. Specific complications have been associated with the accumulation of middle-size toxins, including beta2-microglobulin (12 kDa), myoglobin (17 kDa), prolactin (23 kDa), alpha1-microglobulin (33 kDa), alpha1-glycoprotein (44 kDa), kappa (22 kDa) and lambda (45 kDa) free light chains (FLC). Moreover, mediators of oxidative stress such as asymmetric dimethylarginine, malondialdehyde, oxidative-LDL and inflammatory cytokines such as Interleukin-6 (IL)-6, IL1-β, TNF-α have been involved in atherosclerosis, malnutrition, cardiovascular events and mortality. Hemodialysis (HD) remains the main standard modality of renal replacement therapy in ESRD. In the past decade, low-flux hemodialysis was most commonly used, providing effective clearance of small solutes through diffusion, but negligible clearance of middle molecules. This limitation was insufficiently improved by the development of high-flux (HF) dialyzers due to their cut-off pores size values of approximately 15-20 kDa. In fact, most of middle molecules cannot be efficiently removed by HF-HD because of their molecular radii larger than that of membrane pores. Thus, HF dialyzers were used in post dilution on-line hemodiafiltration (OL-HDF) mode with high convection volumes and achieved greatest clearance of middle molecules. However, OL-HDF is generally not available in most HD centers and needs additional hardware technology. Therefore, several super high-flux (SHF) dialyzers integrating higher cut-off size pore value and achieving Beta2-microglobulin clearance \> 70 ml/min were developed for HD mode. These SHF dialyzers used in HD (SHF-HD) provides similar middle molecules depuration compared to OL-HDF. The recently developed medium cut-off (MCO) dialyzer (Theranova 500™, Baxter healthcare Corporation Deerfield, USA; surface area 2 m², ultrafiltration coefficient: 59 ml/h/mmHg) differs from conventional HF membranes by higher and controlled porosity resulting in a steep sieving curve with a cut-off value approaching that of albumin. MCO-HD has demonstrated efficient depuration of middle uremic toxins as compared to HF-HD, similar to that of OL-HDF. MCO-HD and SHF-HD are two new large pore size dialyzers currently used nowadays in HD. In addition, the interaction between blood and membrane surface play a key role in generating oxidative stress and inflammation. Antioxidants such as vitamin E work by inhibiting LDL oxidation and by limiting cellular response to oxidized LDL. In HD patients, vitamin E may be integrated as a part of the HD procedure in the form of bioreactive dialysis membranes, in which the blood surface has been modified with alpha-tocopherol. Dialysis with vitamin E-coated membranes has been associated with an improvement in biocompatibility including circulating lipid peroxidation biomarkers and cytokine induction. In small studies, vitamin E coated dialyzers have been associated with reduced red blood count fragility and improvements in erythropoietin resistance index and erythropoietin requirements in HD. VieX (Polysulfone, surface area: 2.1 m², sterilization gamma, ultrafiltration coefficient: 104.3 ml/h/mmHg, Asahi Kasei Medical, Japan), a novel SHF vitamin E-coated (SHVE) dialyzer, which has larger pore size than HF dialyzer, might provide higher middle molecules removal and biocompatibility improvement. The aim of the present study was to compare the efficiency of the SHFVE dialyzer (VieX™) versus the MCO dialyzer (Theranova 500™) on the removal of beta2-microglobulin and other middle molecules in a non-inferiority fashion, and their respective effects on inflammation, oxidative stress and biocompatibility parameters.