**7. Future perspectives of dialysis membrane**

With above mentioned technique, we will be able to expect an even better dialysis membrane to come into the market. Several futuristic functions desired for dialysis membrane is also introduced, expecting a new era to come. Followings are the problems to be solved in the future perspectives of dialysis membrane.

#### **7.1. Solute removal performance**

trations were approximately halved or even less from the second to the fifth week. The peak concentration, however, returned back to three folds in the first use of PSf after five-week use

According to another clinical data shown in Figure 16, PSf with PVP(+++) showed highest C3a elevation, followed by PEPA with PVP(++), PVP(+), and PVP(-). The degree of C3a elevation was a function of amount of PVP included in the membrane regardless of the main material

> FDY10 (PEPA, PVP(+)) FDY100 (PEPA, PVP(++)) FLX#1 (PEPA, PVP(-)) FLX#2 (PEPA, PVP(-)) APS-S (PS, PVP(+++)) FX (PS, PVP(+++))

0 60 120 180 240

Time [min]

Figure 16. Time course of C3a change during 4 hr HD treatment in 1 patient Symbols are arranged in the chronological order from the top to the bottom. **Figure 16.** Time course of C3a change during four hr treatment in 1 patient. Symbols are arranged in the chronological

From these results, we learned that PVP may not be the best choice as a hydrophilic agent in

With above mentioned technique, we will be able to expect an even better dialysis membrane to come into the market. Several futuristic functions desired for dialysis membrane is also introduced, expecting a new era to come. Followings are the problems to be solved in the future

of PEPA with PVP(+).

182 Updates in Hemodialysis

of the membrane.

**0**

**100**

order from the top to the bottom.

terms of blood compatibility.

perspectives of dialysis membrane.

**7. Future perspectives of dialysis membrane**

**200**

**300**

C3a change (%)

**400**

**500**

**600**

Since on-line HDF has been gaining popularity in European countries as well as in Japan, HDF with much larger amount of fluid exchange has to be more easily performed for the further success of this modality. Standard on-line HDF in European countries is performed in postdilution system with *Q <sup>B</sup>*=400 mL/min, *Q <sup>D</sup>*=700 mL/min, *Q <sup>F</sup>*=90 mL/min, *Q <sup>S</sup>*=80 mL/min=19.2 L/4hr in single patient dialysis machine (SPDM) system, whereas that in Japan is performed in pre-dilution system with *Q <sup>B</sup>*=250 mL/min, *Q <sup>D</sup>*=500 mL/min, *Q <sup>F</sup>*=260 mL/min, *Q <sup>S</sup>*=250 mL/ min=60 L/4hr in central dialysis fluid delivery system (CDDS) [26] (Figure 17). In terms of solute removal, the difference between these two methods is the largest target solute to be removed, i.e., "European HDF" is targeted to remove β2-MG (MW 11,800) with little loss of albumin (some ten mg/treatment), whereas "Japanese HDF" is targeted to remove α 1-MG (MW 33,000) or even greater ones with albumin "removal" less than 4 g/treatment because enough removal of α1-MG cannot be possible without removing considerable amount of albumin (Figure 13). Although ultra-"super-high flux" dialyzers are commercially available in Japan, termed class V in Japanese reimbursement system, which remove α1-MG to achieve clinically effective reduction rate (> 30 %) [ <sup>26</sup> ] , they also remove considerable amount of albumin (> 5 g/treatment) as well as amino acids, important small solutes from the nutritional point of view. Therefore when more precise prescriptions are necessary, on-line pre-dilution HDF is preferred because it removes α1-MG more than 30 % with albumin loss of 4 g/treatment or less and with considerably reduced clearance for small solutes, including amino acids, due to reduced net dialysis fluid flow rate (net *Q <sup>D</sup>*=500-250=250 mL/min).

Figure 6-1. Comparison of post-dilution and pre-dilution on-line HDF with typical European and Japanese flow rates, respectively **Figure 17.** Comparison of post-dilution and pre-dilution on-line HDF with typical European and Japanese flow rates, respectively.

According to the Italian study [17], on-line HDF/HF is a useful tool for treating patients with dialysis induced hypotension. Then diafilters with higher hydraulic permeability with little albumin loss that do not aim to achieve higher solute removal may be useful for those patients. Not to mention, design specifications of dialyzer/diafilter is as important as the membrane permeability in terms of solute removal under given therapeutic conditions.

#### **7.2. Biocompatibility**

Many classic problems with biocompatibility in the past such as transient leukopenia, complement activation, negative charge syndrome, etc., have already been dissolved by modifying physical and chemical structures of the dialysis membrane. Most currently available synthetic polymeric membranes, however, employ PVP as a hydrophilic agent as well as a pore-forming agent. Study shows that many symptoms including abrupt decrease of blood pressure or shock right after starting treatments could be induced most probably due to PVP included in the membrane, and it is sometimes called "PVP intolerance". Novel hydrophilic agents may be studied for the purpose of replacing PVP. Alternately, novel casting technique in which no hydrophilic agent is necessary has to be studied, knowing that PMMA, EVAL, and PEPA are cast with no additives although they are also originated from petroleum.

#### **7.3. Surface modification and adsorption**

Surface modification with the third substances is another way to obtain membranes with preferred permeability as well as biocompatibility. For example, PSf membrane coated with vitamin E showed a great success for reducing reactive oxygen species (ROS) as well as free radicals that also showed preferable clinical results (Terumo, Asahi-Kasei). Toray introduced a novel technique with NV polymer to their PSf membrane to reduce adsorp‐ tion of cells as well as protein molecules on the membrane. Although both two mem‐ branes work well clinically, they still utilize PVP in the same amount as previously included before. Then it should be noted since surface modification is closely related to solute transport as well as biocompatibility, biomimicry situations under dialysis must be further taken into consideration.
