Selecting a Dialyzer: Technical and Clinical Considerations

Introduction

During hemodialysis (HD), solutes and water are removed through a semipermeable membrane using different separation mechanisms (diffusion, convection, adsorption, and ultrafiltration). The traditional classification scheme for dialysis membranes has been based broadly on composition and water permeability. However, advances in biomaterials and improved fiber production (spinning) technology have led to consideration of several other parameters for membrane characterization, especially new permeability indices.

While the dialysis membrane is the most important determinant of HD performance (i.e., solute clearance), the dialyzer in which it is housed is the device that is actually prescribed by the clinician for treatment. In this chapter, the characteristics of dialyzers used in clinical practice are discussed, with particular attention paid to the parameters that most importantly influence performance. Specifically, the effect of dialyzer design on the mechanisms primarily mediating solute removal, namely, diffusion and convection, is highlighted. While the chapter largely focuses on dialyzer characteristics related to performance, a brief discussion of biocompatibility is also provided. The chapter includes information about newer and emerging applications, with emphasis on therapies designed to remove large molecular weight uremic toxins. The final section summarizes the important considerations for the clinician in selecting a dialyzer.

Hollow Fiber Dialyzers: Fundamental Considerations

The introduction of the hollow fiber artificial kidney revolutionized the field of dialysis in the late 1960s. Relative to its predecessor, the parallel plate dialyzer, the specific advantages of a hollow fiber configuration include an improved surface-to-volume ratio in the blood compartment (shorter diffusion path lengths), along with decreased boundary layer effects and acceptable axial (end-to-end) pressure drops.

With regard to membrane material, dialysis membranes have been categorized traditionally into cellulosic and synthetic groups ( Table 6.1 ). While unmodified cellulosic membranes were used extensively in the past, their utilization has dropped precipitously over the past decades to the current point of effective absence from the market. Although the performance and functional characteristics of some modified cellulosic membranes are similar to those of synthetic membranes, utilization of the former group continues to fall. As such, this chapter largely addresses synthetic membranes.

In preparation for constructing a dialyzer, several thousand (approximately 10,000–17,000) individual hollow fibers are assembled and wound together to form a “bundle” having defined characteristics, including a specific fiber spatial arrangement and packing density ( Fig. 6.1 ). These parameters influence interfiber dialysate flow distribution, an important determinant of dialysate-side mass transfer. After this fiber bundle is inserted into the plastic housing of the dialyzer, additional steps occur, including the application of a polyurethane (“potting”) compound at either end of the bundle to encapsulate the fibers, along with sterilization of the finished dialyzer product. Steam sterilization has gained popularity over the years, while the use of ethylene oxide has fallen. Polyurethane can act as a reservoir for ethylene oxide, resulting in the possibility of clinically relevant amounts of residual ethyl oxide in the dialyzer after pretreatment rinsing.

Although not the focus of this chapter, a few basic principles related to biocompatibility are worth highlighting. The traditional parameter for characterization of dialysis membrane biocompatibility has been complement activation, and one of the original driving forces for the introduction of synthetic membranes was attenuation of this phenomenon (relative to unsubstituted cellulosic membranes). However, other indices have been studied, including those related to cytokine activation, effects on inflammatory cells, and coagulation. Moreover, certain principles generally governing the exposure of flowing blood to a biomaterial apply to the case of HD. First, it is well described that both the inflammatory potential, as measured by cytokine and complement activation along with other indices, and the thrombogenic propensity of a biomaterial are mediated by the nature of the layer of proteins adsorbed instantaneously to the membrane surface. (The effect of protein adsorption on membrane performance is discussed later.) From the perspective of thrombogenicity, the biomaterial literature clearly differentiates low-flow conditions, in which clotting is mediated predominantly by the coagulation pathway, from high-flow conditions, in which shear-induced platelet effects assume an important role. Although not clearly elucidated, both of these phenomena probably influence the thrombogenic potential of a particular dialyzer. Finally, it should be emphasized that the biocompatibility of a treatment is a function of not only the dialyzer but also the entire dialysis system, including the blood tubing and all other biomaterials in the extracorporeal circuit along with the fluid to which the patient is exposed.

Hollow Fiber Membrane Characteristics

Influencing Dialyzer Performance

Based on the spinning process used in the manufacture of hollow fiber membranes for HD, it is impossible to produce a membrane with uniform pore sizes. Nevertheless, one of the major goals of the manufacturing process is to produce a membrane with a relatively narrow distribution of pore sizes around a desired average pore diameter that, in turn, determines the overall solute and water permeability properties ( Fig. 6.2 ). In general, a tight pore size distribution corresponds to a relatively sharp molecular weight cutoff for solute depuration, providing a demarcation between large molecular weight uremic toxin removal and albumin loss for high-flux dialyzers.

From a structural perspective, the wall thickness values for contemporary synthetic membranes generally range from 20 to 50 μm. However, the majority of synthetic membranes used for contemporary HD have an asymmetric structure in which a thin inner “skin” layer (approximately 1 μm or less) at the membrane–blood interface serves as the primary size-discriminating element with respect to solute removal. The remaining wall thickness (“stroma”) acts as a support structure that also provides substantial surface area for molecules that are removed by adsorption. As opposed to the compact nature of the skin layer, the structure of this component of the membrane is relatively open ( Fig. 6.3 ).

In HD, the flow of blood tangential to the membrane surface helps create concentration gradients for diffusive solute removal. Hollow fibers typically have an inner (blood compartment) diameter of approximately 180–220 μm and length of 20–24 cm, resulting in membrane surface areas generally in the 1.5 to 2.5 m ² for most contemporary dialyzers. The major incentive for reducing hollow fiber inner diameter is enhanced diffusive mass transfer due to reduced diffusion path length within the blood compartment. Moreover, the inverse proportionality between channel width and shear rates (at constant flow rates) leads to attenuated blood-side boundary layer effects for smaller diameters. However, there are limits on the extent to which a reduction in inner diameter can be achieved practically due to the resultant increase in flow resistance. When this occurs, a proportional increase in the axial (arterial to venous) pressure drop is required to achieve a specific blood flow rate. In fact, flow resistance is related to the inverse of the fourth power of the hollow fiber inner diameter—as such, a small change in diameter results in a large increase in resistance.

Hydraulic flux (water permeability) has been the most common criterion used traditionally to classify dialysis membranes. The clinical parameter used to quantify water permeability, Kuf (mL/h/mm Hg), is derived from the relationship between ultrafiltration rate (Qf) and transmembrane pressure (TMP) over a clinically relevant range of the latter parameter. The rate of ultrafiltrate flow through membrane pores is roughly proportional to the fourth power of the mean pore radius (i.e., r ) of the membrane at constant TMP. As such, the membrane parameter having the most significant influence on water flux is the average pore size. While the water permeability of a dialyzer is a specific property characterizing a “clean” (i.e., unfouled) membrane, its effective value is dynamically influenced by protein/membrane interactions during the course of a typical treatment, as discussed later.