What are characteristics of coil dialyzers?

Coil dialyzers consist of a cellulose acetate membrane tightly wrapped around a plastic or metal coil and encased in a rigid plastic housing. The coil dialyzer was the first type of dialyzer sold commercially and mass produced, and is known as the dialyzer of the 1950s. The priming volume of the coil dialyzer was very large, ultrafiltration was unpredictable, and blood leaks were quite common.

What are characteristics of parallel plate dialyzers?

Parallel plate dialyzers are assembled in layers, like a sandwich. Sheets of membrane are placed between supporting plates, which have ridges, grooves, or crosshatches to support the membrane and allow the flow of dialysate along it. The blood flows through the sheets of the membrane. The contained volume of blood is small, and heparin requirements are also usually small. A disadvantage of parallel plate dialyzers is that they are compliant. This means that the volume of blood that they hold increases as the transmembrane pressure (TMP) increases. The main disadvantage of parallel plate dialyzers is that they are not well suited for reuse.

What serves as the semipermeable membrane in the hollow-fiber artificial kidney?

Tiny hollow fibers of about 150 to 250 μm in diameter are used. Blood flows through these tens of thousands of hollow fibers. They are formed from a variety of materials, both cellulosic and synthetic. Wall thickness may be as little as 7 μm, although some synthetics have walls of 50 μm or more (Fig. 6-1).

Figure 6-1 Hollow-fiber dialyzer.

What are advantages of hollow-fiber dialyzers?

The contained blood volume is very low in relation to the dialyzer’s surface area because of the dialyzer’s flow geometry. Resistance to blood flow is low because of the large number of blood passages. Hollow-fiber dialyzers are not compliant; therefore, they do not increase in shape or in the volume they hold under high TMP. Ultrafiltration can be precisely controlled. They are well adapted to reuse.

What are disadvantages of the hollow-fiber artificial kidney?

Meticulous deaeration of the fiber bundle is required before beginning a dialysis procedure. Otherwise, fibers may air lock and not admit blood. There may be uneven distribution of blood at the inflow header space, with reduced perfusion of some of the center fibers. Hollow-fiber dialyzers may be sterilized with ethylene oxide (ETO). Residual toxic products of ETO sterilization retained in the potting material of the headers can cause adverse patient reactions. Patient may require higher heparin doses to keep hollow fibers from clotting.

Are there other ways to sterilize hollow-fiber dialyzers?

Yes. Some producers use gamma irradiation. Other manufacturers employ steam sterilization. Both methods are effective. Electron beam, or e-beam, is a newer method of factory sterilization of hollow-fiber dialyzers. Electron beam sterilization involves the use of high-energy electrons to process dialyzers. The DNA chains of the microorganisms become disrupted and are inactivated, which produces a sterile dialyzer. The electron beam does not use chemicals or radioactive materials for its sterilization process and may be a good alternative for the patient who is sensitive to ETO.

What is the nature of a cellulosic membrane?

Cellulose (C₆H₁₀O₅) is a complex carbohydrate polymer that is the structural material of plants. Commercial cellulose is obtained from wood products and cotton. Treatment with heat and chemicals produces a liquid slurry, which is coagulated and formed into sheets or extruded through dies as hollow fibers. Different kinds of processing result in membranes of various thicknesses, water-absorptive qualities, and permeabilities.

What accounts for the permeability of cellulosic membranes?

Electron microscopy shows that the fibers of cellulosic membranes swell when wet, forming a tortuous maze. The “pores” are actually twisting, irregular tunnels that force water or a solute molecule to travel a distance several times the thickness of the membrane to get through it.

What are some cellulosic membranes now used in hemodialysis?

Cuprophan has been widely used. The cellulose is treated with ammonia and copper oxide during manufacture; cuprammonium rayon and Hemophan are modifications. Saponified cellulose ester, cellulose acetate, and triacetate are other widely used cellulose materials.

What are the advantages and disadvantages of cellulosic membranes?

One distinct advantage of cellulosic membranes is the fact that they have been used for many years, and therefore their transport characteristics are well known. They are also relatively inexpensive. However, all cellulosic membranes have some degree of bioincompatibility with blood. This poses a number of problems, which will be discussed later in this chapter.

What are features of synthetic membranes?

The synthetic membranes are thermoplastics. They have a thin, smooth luminal surface supported by a spongelike wall structure. Those used for hemodialysis include polyacrylonitrile (PAN), polysulfone (PS), polyamide, polymethyl methacrylate (PMMA), and others. Convective transfer accounts for their overall mass transport. You will see greater removal of middle and large molecules with these membranes. All have ultrafiltration coefficients of 20 to 70 mL/h/mm Hg or more. They are well adapted to reuse. Synthetic membranes have much fewer bioincompatibility problems than cellulosic membranes.

What are negative aspects of synthetic membranes?

Synthetic membranes have several negative aspects, including the following:

How does one measure the level of inflammatory response resulting from blood-membrane interaction during hemodialysis?

The intensity of the reaction is measured by the level of complement generation following initiation of hemodialysis. Markers used to evaluate complement activation are C3a, C5a, and the “membrane attack complex”—C5b through C9—in the patient’s blood.

What is complement activation?

The complement system is a series of plasma proteins that react sequentially to cause a variety of biologic events. This system works with the immune system to defend the body from substances that the body determines to be “nonself.” When blood encounters a hemodialysis membrane, the response elicited is similar to the one that occurs when the body’s immune system is challenged by bacteria.

What are some of the intradialytic manifestations of complement activation?

The first clinical manifestation to be associated with complement activation is leukopenia. Immediately after starting hemodialysis using cellulosic membrane, patients’ white blood cell (WBC) counts drop sharply. This begins to correct after about 15 minutes. By the end of a four-hour dialysis, the WBC count will have returned to the initial level or perhaps be slightly higher, due to a compensatory response by the bone marrow. This leukopenia is transient, but it may be important to patients with compromised cardiac or pulmonary systems. C5a, an end product of the complement cascade, activates WBCs. When WBCs are activated, they become “sticky.” These cells aggregate, or clump, and are sequestered in the first capillary bed they encounter, usually the lungs. The clumps of WBCs reduce pulmonary capillary perfusion and reduce the patient’s ability to efficiently exchange oxygen and carbon dioxide between blood and alveolar air. This may manifest as intradialytic hypoxemia. Other intradialytic problems likely associated with complement activation include chest pain, back pain, coagulation abnormalities, and, in severe cases, anaphylaxis. Activation of complement peaks at 15 minutes and can last as long as 90 minutes. The amount of complement generated relates to the type and surface area of the membrane being used.

Which membranes induce the highest levels of complement activation?

Cellulose and cellulose-based membranes induce more complement activation than do synthetic membranes (Table 6-1). The chemical composition of the cellulosic surface is similar to that of the cell wall of bacteria: both are chains of polysaccharide structures. The body responds to blood-cellulose contact in much the same way as it does to invasion by bacteria. Free hydroxyl groups on the membrane surface are likely the primary source of the intense complement activation. Chemical alterations to buffer the free hydroxyl groups are used to create “modified cellulosic membranes,” such as cellulose acetate and Hemophan. Membranes of cellulose acetate have some of the surface hydroxyl linked with acetyl groups. Hemophan membranes have amino groups attached to the reactive sites to buffer them. Both of these modifications reduce the amount of complement generated; however, these membranes are still less effective than synthetic membranes in minimizing complement production.

Table 6-1 Types of Dialyzer

Why do synthetic membranes induce less complement activation than cellulosic membranes?

Being synthetic, these membranes lack the reactive sites found on cellulose-based membranes; thus the amount of complement activation generated during hemodialysis is less than with cellulosic membranes.

What are some of the long-term considerations when selecting a membrane for hemodialysis?

Long-term use of bioincompatible membranes may be associated with an increased incidence of infection and malignancy and with impaired nutritional status. Patients dialyzed on cellulosic membranes have a higher incidence of β2-amyloid disease (β2AD) than those dialyzed on synthetic membranes. The increased risk of infection and malignancy is thought to be due to repeated attacks on the patient’s immune system. When patient blood is repeatedly exposed to bioincompatible surfaces, the body responds as though under attack. The immune system kicks in, complement is generated, and the inflammatory response is triggered. There can be tissue damage, and future stimuli may elicit only a limited response, thus predisposing the individual to infection and potential malignancy.

Malnutrition is a major contributor to morbidity and mortality of patients on hemodialysis. Even with adequate protein intake, malnutrition is a problem and seems to relate to an accelerated catabolic process, most evident on dialysis days. A catabolic effect associated with bioincompatible membrane is well documented. However, recent studies have demonstrated an increase in protein catabolism during hemodialysis with synthetic membranes as well (Ikizler et al., 2002). β2AD is important in long-term morbidity. Clinical manifestations include arthropathies, bone lesions and pathologic fractures, soft tissue swelling, and carpal tunnel syndrome. Patients being dialyzed with cellulosic bioincompatible membranes exhibit more pronounced clinical symptoms of amyloidosis (Schiffl et al., 2000). Possible reasons for the difference include the following:

How does membrane biocompatibility affect patients with some residual renal function?

In one study, patients dialyzed on cellulose acetate membranes appeared to lose residual renal function more rapidly than those dialyzed on polysulfone membranes.

Does biocompatibility of the membrane affect patients in acute renal failure?

This is not clear. There is a consensus that the more compatible membranes do contribute to better recovery and survival. Less complement activation, less WBC activation, and less inflammation associated with more biocompatible membranes are believed to be responsible.