Performance of hemodialysis with novel medium cut-off dialyzers

Abstract

Background. Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules. Methods. In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments. Results. MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF. Conclusions. MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.

Modeling of Internal Filtration in Theranova Hemodialyzers

“…ment of a membrane class which displays a unique relationship between extended removal of large MW uremic toxins (up to 45 kDa) and clinically acceptable albumin losses. These attributes have been demonstrated in the literature [26], and clinical results with this membrane class suggest that its depuration capabilities in the HD mode can be equivalent to those of online HDF. As such, the term "expanded HD" has been applied recently to the clinical use of this membrane class [27] .…”

Introductory Chapter

“…However, high-flux dialyzers are limited in their ability to remove larger-size uremic toxin such as κ and λ free light chains. The recent innovation of medium cut-off membranes [19], which has been shown to remove adequate concentrations of different and larger size uremic toxins, including myoglobin, pro-inflammatory cytokines and λ free light chains, are expected to support patients with retention of high contents of uremic toxins, erythropoietin-resistant anemia and malnutrition-inflammation syndrome, and possible positive impact on cardiovascular and all-cause mortality [15,26,28]. This type of dialyzer can be used on regular HD machine with usual blood flow rate (about 300 ml/min), dialysate flow rate (500 ml/min), conventional treated water (bacterial growth <100 U/ml and endotoxin <0.25 EU/ml) and without the need of fluid replacement [28].…”

“…This hemocontrol technique, which is based on an automatic slowdown of ultrafiltration rate, sodium transfer and the release of the vasoconstrictor arginine vasopressor [18], has been used to support patients with excessive fluid retention, especially those who lost their residual renal function and nonadherent to dialytic prescription, and are predisposed to frequent episodes of intradialytic hypotension [14]. The advancement technology of HD machines was accompanied by significant improvement in dialyzers compatibility and membrane permeability (including pore size, density and distribution, length of fibers and its reduced inner diameter), which include high-flux and medium-to-high cut-off membranes [19]. These innovations, together with the ability to provide ultrapure and online treated water by modern water treatment plants, did not only reduce inflammation, erythropoietin resistance and cost reductions [20], but also allowed the implementation of online hemofiltration (HF) and hemodiafiltration (HDF) treatments [21,25] and the use of high-flux dialyzers.…”

Effects of Expanded Hemodialysis Therapy on Clinical Outcomes

“…These membranes have pore sizes which allow the clearance of solutes of up to 45 kDa [31], and whilst albumin loss is greater than HFHD (median 2.9 vs. 0.2 g) and HDF, they are at levels lower than those seen in peritoneal dialysis [32] . The pore size variance is around half that of HRO membranes [33], allowing more selectivity.…”

“…Following exposure to blood, the membrane is less permeable than the glomerular basement membrane [33] . HD with a HRO membrane gives a greater clearance of λFLC (45 kDa in size) when compared with both HFHD and HDF [31] . In addition to this, treatment in HD with an HRO membrane appears to downregulate the expression of both IL-6 and tumor necrosis factor-α mRNA when compared with HFHD.…”