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Insights

Understanding Dialyzer Types

Understanding Dialyzer Types

ANATOMY OF A HOLLOW FIBER DIALYZER

A hollow fiber dialyzer bundle comprises 7–17 x 103 semipermeable hollow fibers
that allow solute and fluid transfer between blood and dialysate. Typical fibers have
an internal diameter of 180–200 microns and wall thickness of 30–40 microns,
yielding 1.0–2.5 m2 of surface area. Fibers may have features, such as undulations,
to distribute dialysate flow evenly through the fiber bundle.

The fiber bundle is enclosed in an outer housing that forms the dialysate
compartment. The header is the space enclosed by the end cap and the
polyurethane potting material that holds the hollow fibers and forms a barrier
between the blood and dialysate compartments. Headers channel blood from the
dialyzer inlet into the membrane fibers and from the membrane fibers into the
dialyzer outlet. The end caps can be removed from some dialyzers. In those cases,
an O-ring is used to form a seal between the end cap and the potting material. Blood
and dialysate flow in opposite directions (countercurrent flow) to maximize diffusive
solute transfer.
MEMBRANE MATERIALS AND BIOCOMPATIBILITY

Non-synthetic membranes are derived from natural materials such as cotton and are
less biocompatible than synthetic membranes. Biocompatibility can be improved by
substituting hydroxyl groups, which reduces the ability of cellulose membranes to
activate complement and cause leukopenia. Moieties that have been substituted for
cellulose include acetate, diethylaminoethyl (DEAE), benzyl, polyethyleneglycolic,
and vitamin E. The resultant membranes are referred to as modified cellulose
membranes. Only cellulose diacetate and cellulose triacetate membranes remain in
widespread clinical use in the U.S. Modified cellulose membranes can be either high
flux or low flux.

Synthetic membranes are commonly used in the U.S. These include:

 PSf (polysulfone and a family of polysulfone blends) offer good biocompatibility and
protection from endotoxins
 PES (polyethersulfone) which is a blend of hydrophobic base polymers with good
biocompatibility and less albumin loss
 CTA (cellulose triacetate) with increased solute permeability especially for beta-2
microglobulin
 PMMA (polymethylmethacrylate) with increased adsorption properties to enhance
removal of some inflammatory molecules
 PEPA (PES plus polyarylate) with enhanced endotoxin protection
 EVAL (ethylene vinyl alcohol copolymers) with low inflammatory impact
  PAN (polyacrylonitrile) with good biocompatibility and enhanced fluid removal due to
hydrophilic properties
DIALYZER PERFORMANCE CHARACTERISTICS

The primary mode for removal of small solutes (e.g., urea) by hemodialysis is
diffusion down the concentration gradient between plasma water and dialysate.
Transfer of small solutes (e.g., HCO3-) from dialysate to plasma water also occurs
primarily by diffusion. The rate of diffusion is a function of the thickness and porosity
of the membrane and the diffusivity of the solute in the membrane. It is expressed as
the diffusion coefficient of the membrane for a given solute. The rate of diffusion is
greatest for small molecules and the diffusivity of a solute in a membrane decreases
logarithmically as solute size increases. The rate of diffusion also decreases as
membrane thickness increases and porosity decreases.

The primary mode for removal of large solutes by hemodialysis is convection, as

water containing these solutes flows from plasma to dialysate in response to a
hydraulic pressure gradient. The rate of convection is a function of the ultrafiltration
rate, size of the solute and pore size of the membrane. The ability of a solute to pass
through the pores of a membrane is expressed as the sieving coefficient of the
membrane for a given solute. A solute with a sieving coefficient of 1.0 passes freely
through the membrane while the membrane is impermeable to a solute with a sieving
coefficient of zero.

Convection provides better removal of large solutes than diffusion because the
decrease in sieving coefficient with increasing solute size is less marked than the
decrease in diffusion coefficient. Dialyzer manufacturers usually provide sieving
coefficients of albumin, beta-2 microglobulin, myoglobin, and lysozyme as
parameters of albumin leak and convective performance.

ADSORPTION AND HYDROPHOBICITY

The nature of the polymers used in a membrane determines the membrane's

tendency to repel water, referred to as hydrophobicity. In general, cellulose
membranes are less hydrophobic while many synthetic polymer membranes are
more hydrophobic. Alloying with hydrophilic polyvinylpyrrolidone (PVP) decreases the
hydrophobicity of the synthetic membrane.

During hemodialysis, proteins may adsorb to both the planar surface of the
membrane and the inner surface of its pores. The adsorbed protein may decrease
diffusive and convective removal of other solutes by effectively reducing the pore size
of the membrane. Hydrophobic surfaces adsorb serum proteins, which can contribute
significantly to low-molecular-weight protein removal by some membranes.

ULTRAFILTRATION COEFFICIENT (KUF)

The ultrafiltration coefficient (Kuf) is a measure of the water permeability of a

membrane and is usually expressed in mL/hr/mm Hg. The formula for determining
Kuf is:

Kuf = QUF (ml/hour)/TMP (transmembrane pressure)

For example, if a dialysis machine generated a transmembrane pressure (TMP) of
200 mm Hg, a dialyzer with a Kuf of 12 ml/hr/mm Hg would produce an ultrafiltration
rate of 12 ml/hr/mm Hg x 200 mm Hg = 2.4 L/hr.

Kuf is relatively unimportant in modern HD machines with volumetric UF control,

although dialyzers with a higher Kuf may have higher clearance and sieving
coefficient values as well.

HIGH PERFORMANCE AND MIDDLE MOLECULAR CUT-OFF MEMBRANES

High performance membrane (HPM) is a classification used in Japan to identify

hollow fiber dialyzers with an advanced level of performance. HPM membranes
increase removal of protein-bound uremic toxins from albumin leak and also increase
removal of middle- to large-molecular-weight solutes, including β2-macroglobulin,
through increased diffusion and adsorption. The Japanese Society of Dialysis
Therapy (JSDT) recommends that pores in HPM be large enough to allow slight
losses of albumin, at a rate of <3 g/session with a blood flow rate of 200 ml/min and a
dialysate flow rate of 500 ml/min. The hypothesis is that larger pores approximate the
glomerular filtration of uremic toxins and albumin in the human kidney, while some
protein leakage may enhance albumin turnover. No clinical outcomes data support
this at present.

DIALYZER CLEARANCE

Diffusive solute removal by a dialyzer is usually described in terms of clearance (K),

which is defined as the volume of blood completely cleared of a given solute per unit
time. Unlike the in-vitro clearance of a specific solute (KoA), which is supplied by the
manufacturer and determined in vitro, K is dependent on both the blood and dialysate
flow rates. For this reason, it is not a good means of characterizing innate dialyzer
performance. All dialyzers report in-vitro clearance values, and the actual in-vivo
clearances are typically lower than the in-vitro values for the same blood flow rate
(Qb) and dialysate flow rate (Qd) combination.

DIALYZER SELECTION

Kt/Vurea is the most validated and commonly measured parameter of dialysis

adequacy despite its limitations1. Some clinicians use a low-efficiency dialyzer and/or
shorter time and low blood and dialysate flow rates during the initial hemodialysis
treatment(s) to avoid dialysis disequilibrium syndrome. In order to determine the
dialyzer that will provide a target Kt/Vurea first calculate the total body water (TBW =
Urea volume of distribution) either anthropometrically (e.g., Watson for adults, Mellits-
Cheek for children) or, preferably, via bioimpedance spectroscopy (BIS) when
available to solve the Kt/V equation for either t (duration of treatment) or K (dialyzer
clearance for a given Qb/Qd).

For example, Mr. Doe has a V of 40L and the target Kt/V is 1.4:
 Kxt/V or Kxt/40 = 1.4

Kxt = 40 x 1.4 = 56 L or 56,000 ml

Let's assume you have a dialyzer that has in-vitro Kurea of 250 ml/min at Qb/Qd of
300/500 ml per minute. This clearance should be multiplied by 0.85, which is about a
15% adjustment from in-vitro to in-vivo clearance. Therefore, K would be 250 x 0.85
= 212.5 ml/min.

The duration of treatment, or t, can now be determined:

212.5 x t = 56,000

t = 56,000/212.5 = 264 minutes (4 hours 24 mins). This time can be

reduced by choosing a bigger dialyzer or increasing Qb and Qd.

On the other hand, if you know the duration of treatment that you are going to
prescribe (let's assume 4 hours or 240 minutes), you can solve for the Kurea needed
to deliver Kt/Vurea of 1.4.

K x 240 = 56,000

K = 56,000/240 = 233 ml/min

In-vitro to in-vivo conversion = 233/0.85 = 274 ml/min

So, you will need a dialyzer with published in-vitro urea clearance of 274 ml/min at a
Qb/Qd of 300/500 ml/min for this patient.

It is important to recognize a few points about these calculations:

1. You can have different Qb/Qd, such as 400/600 or 500/800 ml/min, and should use
them in these calculations.
2. Anthropometric TBW calculations overestimate V, therefore, the delivered
Kt/Vurea may be higher than the calculated one.
3. Total delivered dose may have a contribution from residual kidney function, which is
not accounted for in these calculations.
4. At best, this calculation provides you with a starting point, and adjustments might be
needed based on the measured Kt/Vurea lab values.
5. Currently, there is no evidence to suggest that adequacy targets should be modified
for different etiologies of ESRD, except in special circumstances such as pregnant
patients who need more frequent or daily HD with additional adjustment to the
dialysate composition given their special physiological needs.
6. It would be prudent to avoid delivering high clearances in patients with liver failure or
others who may be at higher risk of increased intracranial pressure such brain trauma
or surgery.