A New Polysulfone Membrane Dialyzer, NV, with Low-Fouling and Antithrombotic Properties.

BACKGROUND: The biggest problem in routine hemodialysis therapy is possibly the blood pressure fall experienced by patients during dialysis. In contrast, in medium- and long-term hemodialysis therapy, the main problem might be deterioration of arteriosclerosis because of medial calcification associated with dialysis vintage. Both problems are caused by an autonomic imbalance or structural change in the blood vessels. Inflammation due to extracorporeal blood circulation is another possible cause. This inflammation is considered to cause platelets activated by contact and adherence with the membrane surface to aggregate with white blood cells and attack the endothelium of the blood vessels. Therefore, we tried to develop a new membrane with no adsorption and no platelet activation. SUMMARY: Polysulfone (PS) membranes with polyvinylpyrrolidone (PVP) as a hydrophilic agent are widely used in dialysis, but blood components adhere to the membrane surface. We developed a new dialyzer, NV, by localizing a new hydrophilic polymer onto the inner surface of a hollow-fiber membrane composed of PS and PVP. The number of platelets that adhered to the NV membrane surface drastically decreased to 0.9% of that with the conventional PS dialysis membrane. We also confirmed the mechanism by which NV realizes clinical improvements in blood pressure drops and inflammation during dialysis, and verified its clinical appeal. Key Messages: The new membrane NV, which inhibits platelet adhesion and is compatible with blood vessels, is clinically beneficial.

A New Poly(Methyl Methacrylate) Membrane Dialyzer, NF, with Adsorptive and Antithrombotic Properties.

BACKGROUND: Poly(methyl methacrylate) (PMMA) membranes adsorb several kinds of proteins and can remove high-molecular-weight proteins, including uremic toxins, which are not removed efficiently by hemodialysis or hemodiafiltration. However, the antithrombogenicity of PMMA membranes is insufficient due to their adsorptive properties. SUMMARY: Coagulation during hemodialysis occurs because proteins that are adsorbed to the PMMA membrane undergo structural changes and are recognized by platelets, which are then activated by adhesion to the membrane surface. In developing a new PMMA membrane dialyzer, NF, we intended to inhibit platelet adhesion to the membrane surface by suppressing the structural change in the proteins adsorbed on the membrane. In addition, we give examples of clinical trials of the NF in Japan and describe its advantages. Key Message: PMMA membrane dialyzers have been used for 40 years. The PMMA dialyzer NF can suppress the adhesion of platelets to the membrane while maintaining protein adsorption.

Trial use of a polymethylmethacrylate membrane for the removal of free immunoglobulin light chains in dialysis patients.

Background. Free immunoglobulin light chains (FLCs) accumulate at high levels in the blood of dialysis patients and are likely to cause immunodeficiency during periods of dialysis. Our group examined the blood FLC concentration, κ/λ ratio and rates of FLC removal in different dialysis modes using different dialysis membranes. Methods. Polymethylmethacrylate (PMMA) membrane (BG-PQ, Toray) under the haemodialysis (HD) condition was used for seven chronic maintenance dialysis patients who had been treated by hemodiafiltration (HDF) (five polyester-polymer alloy (PEPA) and two polysulphone) in a crossover fashion. FLCs in serum were measured with a FREELITE™ Human Kappa Free Kit and Lambda Free Kit prepared by Binding Site, UK (supplied by Medical & Biological Laboratories Co., Ltd, Japan). Each κ-type and λ-type FLC was quantitatively measured with a Dade Behring BNII™. Western blotting was conducted using a goat anti-human κFLC polyclonal antibody. Results. The κ and λ serum FLCs in HD patients (n = 7) were 157.4 ± 88.9 and 121.9 ± 56.3 mg/L, respectively, and were accumulated in concentrations 4- to 16-fold higher than the concentrations in healthy controls. The κ/λ ratio was included in the reference range (0.26-1.65). In the HD cases dialysed with PMMA membrane, the FLCs were removed mainly by adsorption, leaving only very small quantities in the whole dialysis waste fluid. The ratio between the total removed quantity and albumin leakage ((κ+λ)/Alb) was higher in the PMMA HD group than in the HDF group, and the rate of κFLC removal was higher than the rate of λFLC removal. The serum κFLC in dialysis patients had a multimer structure. In western blotting, the adsorbed κFLC (including multimer structure) detected in the PMMA membrane exceeded that detected in the dialysate with the polysulphone membrane. Conclusions. Although the FLCs were removed at high rates under the HDF condition, they were also effectively removed by adsorption with the PMMA membrane under the HD condition. It may be possible to effectively remove the FLC multimer with a PMMA membrane via adsorption. In future studies on FLC removal in patients with chronic renal failure, it will be necessary to assess not only the quantity of simple removal from the blood but also the qualitative properties, such as the degree to which accumulation and removal rates depend on the κ/λ ratio and multimer structures.

Adsorption of Bence-Jones protein to polymethylmethacrylate membrane in primary amyloidosis.

Primary amyloidosis is an incurable disease though high dose melphalan chemotherapy sometime achieves some efficacy in certain patients. The success of the melphalan chemotherapy appears to be associated with reduction of amyloidogenic immunoglobulin light chain (Bence-Jones Protein; BJP). Thus, in an attempt to reduce the BJP load, we conducted adsorption of BJP using polymethylmethacrylate (PMMA) membrane in a patient with primary amyloidosis suffering nephritic syndrome, who chose not to receive high dose melphalan chemotherapy. Following adsorption, the patient reported an improvement of sensory disturbance in fingers. This was confirmed by markedly improved sensory nerve action potential. Western blot analysis of patient's serum also revealed a significant reduction of both multimer and monomer of BJP following adsorption using the PMMA membrane. These results suggest that removal of BJP by PMMA membrane could serve as an alternate therapeutic method in the treatment of primary amyloidosis.