Overview of the hemodialysis apparatus

INTRODUCTION — For patients with end-stage kidney disease, kidney replacement therapy is achieved by dialysis (hemodialysis or peritoneal dialysis) or kidney transplantation. Although true and complete replacement of kidney function is not provided by dialysis, this modality removes metabolic wastes and excess body water and replenishes body buffers in order to sustain life.

The apparatus used to conduct hemodialysis consists of the following components:

●Dialyzer

●Dialysis solution (dialysate)

●Tubing for transport of blood and dialysis solution

●Machine to power and mechanically monitor the procedure

This topic will provide an overview of the hemodialysis apparatus.

GENERAL PRINCIPLES OF DIALYSIS — Prior to discussing the different components of the hemodialysis apparatus, it is helpful to briefly review the principles underlying solute and fluid removal in hemodialysis.

Solute clearance — Solute is cleared from the intravascular compartment by either diffusive or convective transport. Such transport depends upon multiple factors, including the concentration gradient between the blood and dialysate for a particular solute, the type and amount of blood and dialysate flow, the properties of the dialysis membrane, and the size and physicochemical property of the solute being removed.

Diffusive transport — Diffusive transport is the primary means of metabolic waste removal in patients undergoing hemodialysis. Such transport depends upon the interface of blood from the patient with dialysate fluid, which occurs via its flow through pores located within each fiber of the dialysis membrane. Diffusive transport occurs when blood flowing within each hollow fiber meets dialysate fluid bathing the fibers. Diffusion of solutes proceeds down a concentration gradient from blood to dialysate or from dialysate to blood (bidirectional).

The degree of diffusive transport is a function of the concentration difference of the solute with respect to blood and dialysate, membrane surface area, porosity and thickness of the membrane, molecular size of the solute, and flow rate of blood and dialysate. The mass transfer coefficient (KoA) of a dialyzer, which defines its capacity, varies with the depth and porosity of the membrane, the molecular size of a given solute, and the flow rates of blood and dialysate [1]. (See 'Mass transfer-area coefficient (KoA)' below.)

Blood and dialysate flow in opposite directions through the dialyzer with dialysate flow rates generally set at one and a half to two times the blood flow rates, equating to rates of 300 to 500 mL/min and 500 to 800 mL/min for blood and dialysate flow rates, respectively. Such countercurrent flow is integral to maximizing the diffusive clearance of metabolic waste solutes (figure 1). If blood and dialysate flow in the same direction across the dialysis membrane (concurrent flow), the diffusion of a solute will lower the concentration of the substance in the blood and raise it in the dialysate, thereby gradually decreasing and perhaps even abolishing the concentration gradient that would otherwise favor further diffusion. This effect is minimized with countercurrent flow. In this arrangement, the concentration of solute in the dialysate is lowest when it enters the dialyzer at the blood (venous) outflow (where the solute blood concentration is at its minimum) and is highest when it leaves the dialyzer at the blood (arterial) inflow (where the solute blood concentration is at its maximum). As a result, a high concentration gradient is maintained for the length of the fluid paths.

Convective transport — With high rates of fluid transport (ie, ultrafiltration) from blood to dialysate, convective transport of solute also occurs, thereby augmenting diffusive solute transport. In this mechanism, solutes are effectively dragged along with the fluid as it moves across the membrane, depending upon their size relative to the size of the membrane pores.

The propensity for impedance of any solute is described by the sieving coefficient, a numerical assessment of the potential for convective transport of a given solute. This coefficient equals the ratio of the solute concentration in the filtrate to that in the arterial plasma. A sieving coefficient of 1 denotes a solute that passes completely unimpeded whereas a solute that is completely rejected has a coefficient of 0. Very large and small solutes therefore have sieving coefficients approximating 0 and 1, respectively. For small solutes, such as urea, glucose, and electrolytes, the solute concentration in the fluid removed by convective transport is similar to that in the plasma. Since the capacity for small-solute diffusion is generally much greater than that for large-solute diffusion (eg, vitamin B12), the relative contribution of convection may be most important in large-solute transport [1].

These relationships apply to conventional hemodialysis. A different process of solute removal is used with venovenous hemofiltration, in which very large volumes of water and solutes are removed by convection. (See "Continuous kidney replacement therapy in acute kidney injury", section on 'Definition of CKRT modality'.)

Flow rates — The clearance of solutes, either via diffusion or convective transport, is influenced by blood and dialysate flow rates. Increases in clearance occur with increases in flow rates until a plateau is reached; beyond this threshold, no further increases occur with increasing flow. The flow dependence of diffusive transport is greatest for small solutes (eg, urea and electrolytes). These solutes are rapidly cleared, thereby diminishing the concentration gradient for further diffusion. Providing fresh plasma (with a high-solute concentration) and fresh dialysate (with a low-solute concentration) maximizes solute removal.

Small-solute clearances reach a plateau at higher flow rates than large solutes [1]. Since larger solutes diffuse more slowly, the concentration gradient is maintained, and it is the duration of dialysis that is a major determinant of solute removal.

Fluid removal — Fluid removal occurs via a hydrostatic pressure gradient across the membrane, which is generated by the dialysis machine. This transmembrane pressure (TMP) causes fluid to cross from the side of high pressure (blood compartment) to the side of low pressure (dialysate compartment), thereby allowing fluid removal from the patient. This filtering of cell-free fluid from the blood compartment to the dialysate compartment is called ultrafiltration. Permeability is a function of thickness and pore size and varies with dialyzer make and model.

Positive pressurization of the blood compartment coupled with negative pressure (applied) suction to the dialysate compartment establishes TMP. The TMP is set for each patient at each dialysis treatment so that fluid can be removed at a desired volume over a designated time. (See 'Ultrafiltration coefficient (KUf)' below.)

DIALYZERS — Dialyzers are composed of a polyurethane capsule or shell, within which hollow fibers or parallel membrane plates are suspended in dialysate. The fibers or plates function as a semipermeable membrane across which blood and dialysate flow. By crossing this membrane, solutes and water move between a patient's intravascular compartment and the dialysis fluid contained within the dialyzer (figure 1).

Hollow-fiber (also called capillary) dialyzers are the most common dialyzers in current use [2]. Parallel-plate dialyzers are no longer in common use.

The choice of dialyzer should be guided by measures of dialysis adequacy, the perceived need for biocompatibility, and particular patient characteristics. (See "Prescribing and assessing adequate hemodialysis".)

Types of membranes — There are multiple types of membranes used to manufacture dialyzers [3]:

●Cellulose – Unmodified cellulose, also called cuprophane, is a polysaccharide-based membrane obtained from pressed cotton. It is composed of chains of glucosan rings with abundant free-hydroxyl groups.

●Substituted cellulose – Substituted cellulose membranes are obtained by chemical bonding of a material to the free-hydroxyl groups at the surface of the cellulose polymer. The most common type is cellulose acetate, in which acetate replaces 80 percent of the hydroxyl groups.

●Cellulosynthetic – Cellulosynthetic membranes are modified by the addition of a synthetic material (such as diethylaminoethyl in the production of hemophane) to liquefied cellulose during its formation.

●Synthetic – In general, noncellulose synthetic membranes have a higher permeability and are more biocompatible than the cellulose membranes. There are also some synthetic low-flow membranes. A variety of synthetic membranes are available including polyacrylonitrile (PAN), polysulfone, polycarbonate, polyamide, and polymethylmethacrylate (PMMA) membranes.

Concerns related to lower permeability and bioincompatibility have effectively driven cellulose membranes from the North American market, leaving substituted cellulose, synthetic cellulose, and noncellulose membranes as the dominant membranes. (See 'Biocompatibility' below.)

The impact of dialyzer membrane type on outcomes was evaluated in a large cohort study using data from a nationwide Japanese registry of patients on hemodialysis for at least two years [4]. Compared with polysulfone, all-cause mortality at two years was lowest with polyethersulfone and polymethylmethacrylate and highest with cellulose triacetate, ethylene vinyl alcohol, polyacrylonitrile, and polyester polymer alloy. Additional study is needed to assess the potential for improving prognosis with dialyzer type. (See "Clinical consequences of hemodialysis membrane biocompatibility".)

Biocompatibility — Biocompatibility with blood is an important property inherent to the type of dialyzer membrane. During dialysis, contact of blood with the dialysis membrane can incite an inflammatory reaction and activate the complement system, an interaction known as bioincompatibility. While all membranes activate complement to some degree, unmodified cellulose membranes are considered the most bioincompatible. Complement activation occurs to a lesser extent with the more biocompatible substituted cellulose, cellulosynthetic, and synthetic membranes. (See "Biochemical mechanisms involved in blood-hemodialysis membrane interactions", section on 'Complement activation'.)

It is not clear whether long-term use of biocompatible membranes is associated with better quality of life and/or improved survival when compared with bioincompatible membranes. Two controlled trials performed in patients on dialysis, including the Hemodialysis (HEMO) study, did not find any benefits with biocompatible versus bioincompatible membranes [3,5,6].

The impact of specific modifications to the cellulose membrane on inflammation continues to be a subject of ongoing research [7-9].

Flux — Flux refers to the permeability of the dialyzer membrane. High-flux membranes, compared with low-flux membranes, have larger pores with increased permeability, particularly to larger molecules. The flux of a dialyzer is defined by its clearance of beta2-microglobulin, with rates of <10, 10 to 20, and >20 mL/min denoting a low-, mid-, and high-flux membrane, respectively. In Japan, super high-flux membranes with clearances of 50 to 70 mL/min or >70 mL/min are also available [10]. (See "Dialysis modality and patient outcome", section on 'High-flux and high-efficiency hemodialysis'.)

Medium cutoff (MCO) dialyzers have become available for use in conventional hemodialysis [11,12]. These dialyzers have a larger pore size that is designed to improve middle molecule clearance without promoting the loss of albumin into the dialysate [12]. However, one prospective cohort study of 57 patients dialyzed with either MCO or standard high-flux dialyzers found no difference in the serum levels of middle molecules or albumin between the groups over one year [13]. Another longitudinal crossover study of 89 patients dialyzed with MCO for 24 weeks between two four-week periods of high-flux dialysis showed no reduction in albumin levels and no effects on quality of life or restless leg symptoms [14]. The benefits of dialyzers with the capacity for such large solute removal may be limited to certain clinical situations, and their use in clinical practice remains a topic of investigation.

High cutoff (HCO) dialyzers have large pore sizes that permit the efficient passage of proteins as large as 25 to 50 kilodaltons. These dialyzers are not used for conventional hemodialysis but have been used as an extracorporeal method of light chain removal in patients with multiple myeloma and light chain cast nephropathy. HCO dialyzers are not commercially available in the United States but are available in Europe. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Treatment and prognosis", section on 'Extracorporeal methods for light chain removal'.)

Specifications

Ultrafiltration coefficient (KUf) — The ultrafiltration coefficient (KUf) is a measure of the dialyzer's permeability relative to water. The KUf is the volume of fluid (in mL/hour) that is transferred across the membrane per mmHg of transmembrane pressure (TMP). Thus, the ultrafiltration rate per hour is the product of the KUf and the TMP.

A low KUf denotes a low permeability to water. The lower the permeability to water, the higher the TMP needed to achieve ultrafiltration. Conversely, dialyzers with higher KUf specifications achieve desired ultrafiltration volumes with lower TMPs, and volume removal is achieved by ultrafiltration that is controlled so as to avoid excessive volume losses.

Contemporary machines require only that desired fluid loss for the treatment be entered into the machine. If intradialytic symptoms of hypotension or hypovolemia develop, then the ultrafiltration goal can be modified to minimize such symptoms. Technologies to measure intradialytic changes in intravascular blood volume continue to evolve. Continuous hematocrit monitoring, which monitors absolute hematocrit and oxygen saturation, can be achieved by way of a simple device that is built into dialysis machines [15]. The apparatus consists of a small cuvette that is attached to the arterial side of the dialyzer and determines the hematocrit concentration via optical measurements. Continuous hematocrit monitoring has been reintroduced on a large scale in the United States but is not universally used in every center.

Mass transfer-area coefficient (KoA) — Clearance of various solutes from blood is a function of dialyzer efficiency. Dialyzer clearances are routinely reported as urea or creatinine clearances (small solutes) as well as vitamin B12 (large solute) clearances. The reported clearance of urea by the manufacturer, although most commonly higher than that observed with dialysis, may be used to compare different dialyzers. The clearance of urea is usually reported as that observed at blood flows of 200, 300, and 400 mL/min.  

The mass transfer-area coefficient (KoA), the quantitative measure of a particular dialyzer's efficiency of clearance, is defined by membrane porosity and thickness, solute size, and flow rate of blood and dialysate. The KoA for urea generally varies from 200 to 1100 among the various different dialyzers available [2]. The KoA for a particular dialyzer should be the measurement observed at a blood flow rate of 300 to 400 mL/min. Some investigators suggest that this measure can be utilized to help guide the initial choice of dialyzer in certain clinical settings [2]:

●Small patients and those undergoing dialysis for acute kidney injury (in which gradual solute removal is initially desirable) may be treated with a dialyzer with a KoA <300, with gradual advancement to a more efficient dialyzer. (See "Dialysis disequilibrium syndrome".)

●Patients undergoing chronic hemodialysis therapy may be treated with a dialyzer with a KoA between 300 and 600.

●Individuals requiring high-efficiency dialysis, such as larger-sized patients, may be treated with dialyzers with KoAs >600.

Surface area — The surface area of most dialyzer membranes ranges between 0.8 to 2.1 m². Dialyzers with larger surface areas normally have high urea clearances; however, the efficiency of the dialyzer, as described by the KoA, is most integral to achieving optimal urea clearance, independent of a dialyzer's surface area. (See 'Mass transfer-area coefficient (KoA)' above.)

Priming volume — The priming blood volume required to fill hollow-fiber dialyzers is less than that of parallel-plate dialyzers. In addition, unlike some parallel-plate dialyzers, the blood volume capacity of hollow-fiber dialyzers is essentially fixed and will not increase with increasing TMP. Priming volume depends upon dialyzer surface area and ranges from 60 to 120 mL, excluding priming volume of blood lines, which adds between 100 and 150 mL. The total priming volume therefore ranges from 160 to 270 mL [16]. Lower priming volumes are desirable to minimize the risk of hemodynamic compromise.

Sterilization and reuse — Most dialyzers are sterilized by the manufacturer with ethylene oxide. In the rare instance when allergic reaction to the sterilant is suspected, a dialyzer sterilized by the manufacturer by gamma irradiation or steam autoclaving may be used (see "Reactions to the hemodialysis membrane"). Hollow-fiber membranes are easy to handle, sterilize, and reuse, though the practice of reuse is now rare in the United States. Parallel-plate dialyzers are less easy to reuse but may be less expensive [2,16]. (See "Reuse of dialyzers".)

DIALYSIS SOLUTION — Dialysis machines mix different components with water to produce the final solution of dialysate.

Water — Water used for hemodialysis should comply with established quality standards to ensure patient safety. (See "Assuring water quality for hemodialysis".)

The exposure of patients on dialysis to certain contaminants frequently found in water may result in significant complications, including central nervous system dysfunction, bone disease, hemolysis, infection, and death. These contaminants, the clinical manifestations of toxicity, and the safe levels of those contaminants are presented separately. (See "Contaminants in water used for hemodialysis".)

Components of the dialysate — Typical hemodialysate contains sodium, potassium, bicarbonate (or other buffer), calcium, magnesium, chloride, and glucose (table 1).

●Sodium – Historically, the dialysate sodium concentration has ranged from the mid-130s to as high as 149 mEq/L [17], a level at which intradialytic symptoms associated with osmolality-induced fluid shifts (dizziness, nausea, cramping, fatigue, vomiting) are minimized. More recently, a lower-dialysate sodium concentration and one that is individualized based on the patient's sodium level have been advocated [17-19]. A dialysate sodium concentration between 134 and 138 mEq/L was associated with maintenance of lower interdialytic weight gains in one group of patients on nocturnal dialysis [17].

In addition, the prescription of a blanket dialysate sodium concentration for all patients has been challenged by proponents of an individualized approach [18,19] based on a dialysis sodium gradient of close to 0 [17,20,21]. It has been suggested that sodium "modeling" or "ramping," in which the dialysate sodium concentration is decrementally reduced from 155 to 140 mEq/L during dialysis, might provide even better hemodynamic control [22]. However, this technique has not been universally successful and is generally not advocated, because of its propensity to worsen interdialytic thirst and fluid (weight) gain [23-25]. (See "Intradialytic hypotension in an otherwise stable patient".)

●Potassium – Several dialysate potassium concentrations are available. Dialysate potassium concentrations of 2 mEq/L or greater are commonly used. Concentrations of <2 mEq/L have fallen out of favor, even for patients with very high predialysis potassium levels, because of concerns for sudden cardiac death thought to be related to a very rapid decline in plasma potassium concentration [26]. (See "Acute hemodialysis prescription", section on 'Choice of dialysate potassium concentration'.)

●Bicarbonate – Bicarbonate has replaced acetate as the typical source of buffer in dialysis solution. This is largely due to the association of acetate with cardiovascular instability [27]. (See "Intradialytic hypotension in an otherwise stable patient".)

In many machines, the bicarbonate concentration can be varied from 35 to 40 mEq/L, as dictated by individual patient lab values. The buffering capacity of the various available bicarbonate products is not identical, and, while all bicarbonate-based dialysis products deliver additional buffer, the desired amount of total buffer delivered should be assessed in the context of the individual patient. Historically, bicarbonate has been supplied from a central delivery source; some newer machines are equipped with their own source of sodium bicarbonate in the form of a powder that is automatically mixed with water to produce a saturated solution, which is proportioned with water and acid to achieve the prescribed dialysate for a given patient [28].

The total buffer concentration equals the prescribed bicarbonate concentration plus the acetate contained within the acid concentrate of the particular product being used. High dialysate bicarbonate concentrations can accelerate potassium lowering during dialysis as well as rapid intradialytic changes in potassium and calcium, which can lead to cardiac irritability and fatal arrhythmias [29,30].

●Calcium – Hypercalcemia has become more frequent with the combined use of oral calcium salts for phosphorus binding and calcitriol (1,25 dihydroxyvitamin D3) to suppress hyperparathyroidism. As a result, a calcium concentration of 2.5 or 2.25 mEq/L has replaced the 3.5 mEq/L concentration as the standard dialysate in most hemodialysis units. (See "Management of hyperphosphatemia in adults with chronic kidney disease".)

DIALYSIS TUBING — Inlets for inflowing (undialyzed) blood and fresh dialysate are present in the dialyzer capsule, as well as outlets for outflowing (dialyzed) blood and spent dialysate (dialysis effluent). Synthetic tubing designated as the "arterial" line carries blood from the arteriovenous access to the dialyzer, where blood and dialysate interface at the membrane. A "venous" line simultaneously carries dialyzed blood back to the patient (figure 1). Specialized tubing is now available to facilitate assessment of dialysis access flow in real time while dialysis is ongoing [31].

DIALYSIS MACHINES — A machine to empower and monitor the safety of hemodialysis must include a blood pump to move blood between patient and the dialyzer, a delivery system to transport dialysis solution, and monitoring devices. Pressure monitors, located proximal to the blood pump and distal to the dialyzer, guard against excessive suction of blood from and excessive resistance to blood return to the patient's vascular access site. Many machines also have the capacity to measure on-line clearance. (See "Clinical monitoring and surveillance of hemodialysis arteriovenous grafts to prevent thrombosis", section on 'Static venous dialysis pressure' and "Clinical monitoring and surveillance of the mature hemodialysis arteriovenous fistula".)

Additional monitoring devices include the following:

●A venous air trap and air detector distal to the venous pressure monitor prevent air that may have inadvertently entered the blood circuit from being returned to the patient.

●Proper proportioning of solute (including electrolyte) concentrate to water is monitored by a continuous measurement device.

●A temperature sensor for continuous temperature monitoring of the dialysis solution.

●Dialysate urea sensor that measures urea concentration in the spent dialysate at various times throughout the dialysis treatment. This information can be used to generate a dialysate-side equivalent to the Kt/V. (See "Prescribing and assessing adequate hemodialysis".)

Some of the clinical consequences that may occur because of machine malfunction are presented separately. (See "Acute complications during hemodialysis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hemodialysis (The Basics)")

●Beyond the Basics topics (see "Patient education: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)" and "Patient education: Hemodialysis (Beyond the Basics)")

SUMMARY

●Overview – The hemodialysis apparatus consists of a dialyzer, dialysis solution (dialysate), tubing for transport of blood and dialysis solution, and a machine to power and mechanically monitor the procedure. (See 'Introduction' above.)

●Dialyzers – Dialyzers are composed of a polyurethane capsule or shell, within which hollow fibers or parallel membrane plates are suspended in dialysate. The fibers or plates function as a semipermeable membrane across which blood and dialysate flow in opposite directions. Hollow fibers are the most common dialyzers in use.

•Membrane types and biocompatibility – Dialyzer membranes include unmodified cellulose, substituted cellulose, cellulosynthetic, and synthetic noncellulose. Synthetic membranes are more biocompatible than the cellulose membranes and include polyacrylonitrile (PAN), polysulfone, polycarbonate, polyamide, and polymethylmethacrylate (PMMA) membranes. (See 'Types of membranes' above and 'Biocompatibility' above.)

•Flux – Flux refers to the permeability of the dialyzer membrane and is defined by its clearance of beta2-microglobulin. High-flux membranes, compared with low-flux membranes, have larger pores with increased permeability, particularly to larger molecules. (See 'Flux' above.)

•Specifications – Important dialyzer specifications include the ultrafiltration coefficient (KUf; a measure of a dialyzer's permeability relative to water), mass transfer-area coefficient (KoA; the quantitative measure of a dialyzer's efficiency of clearance), and surface area (ranges between 0.8 to 2.1 m² for most dialyzers). (See 'Specifications' above.)

●Dialysate solution – Dialysis machines mix different components with water to produce the final solution of dialysate. Typical hemodialysate contains sodium, potassium, calcium, magnesium, chloride, bicarbonate, and glucose. (See 'Dialysis solution' above.)

●Dialysis tubing – Dialysis tubing consists of synthetic tubing designated as the "arterial" line, which carries blood from the arteriovenous access to the dialyzer, where blood and dialysate interface at the membrane, and the "venous" line, which carries dialyzed blood back to the patient. (See 'Dialysis tubing' above.)

●Dialysis machine – The dialysis machine must include a blood pump to move blood between patient and the dialyzer, a delivery system to transport dialysis solution, and monitoring devices. Monitoring devices include pressure monitors that detect excessive suction or resistance of blood flow, a venous air trap and air detector that prevent air from being returned to the patient, continuous measurement devices that monitor solute concentrate, dialysate temperature monitors, and a dialysate urea monitor. (See 'Dialysis machines' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jean L Holley, MD, FACP, who contributed to an earlier version of this topic review.