Chapter 50. Hemodialysis

The major forces responsible for solute transport across the membrane are diffusion and convection. Diffusion is influenced by the concentration gradient of the solute, the solute characteristics (eg, molecular weight and charge), and the membrane characteristics (eg, pore size and number). Removal of solutes by diffusion is enhanced by a large concentration gradient, small solute size, and a membrane with a large surface area and many large pores. The concentration gradient is maximized by using countercurrent flow of blood and dialysate.

In convection, hydrostatic or osmotic pressure forces water across the membrane. The water transport facilitates the passage of solutes across the membrane. The term ultrafiltration describes the solute and fluid removal via convection.

In hemodialysis, the predominant mechanism for solute removal is through diffusion, with a smaller amount of solute clearance occurring by convection. Thus, hemodialysis is very effective in removing solutes of small-molecular-weight, but is relatively inefficient in removing solutes of larger sizes. In addition, hemodialysis is an inefficient means of removal of protein-bound substances. Only the free portion of these solutes can diffuse across the membrane and be removed. The removal rate of protein-bound compounds thus depends on the concentration of the unbound solute, the size of the protein, and the replacement rate of the unbound solute.

In hemofiltration, the predominant mechanism for solute removal is through convection; thus, this procedure has the ability to remove solutes of larger molecular size when coupled with a dialysis membrane with a large pore size.

Indications for Starting Chronic Dialysis Therapy

Patients should be considered for initiation of chronic hemodialysis therapy once the estimated glomerular filtration rate (GFR) is less than 15 mL/minute. In most patients, the four variables in the Modification of Diet in Renal Disease (MDRD) equation can be used to estimate the GFR. A 24-hour urine collection for creatinine and urea should be considered in those patients who have reduced muscle mass due to medical conditions such as amputations or limitation on mobility due to congestive heart failure, claudication, chronic lung disease requiring oxygen therapy, etc. There are no randomized trials that suggest an optimal time to initiate chronic dialysis therapy, so clinical judgment is important in making this decision in individual patients.

Earlier Initiation of Dialysis

There are specific indications for starting chronic hemodialysis therapy at a level above a GFR of 15 mL/minute. These conditions include intractable fluid overload not responsive to diuretics, hyperkalemia unresponsive to medical therapy, metabolic acidosis not fully corrected by medical therapy, malnutrition or weight loss not ascribed to other medical conditions, or decreasing functional status. It may also be desirable to start home dialysis therapies at a higher level of GFR to minimize training difficulties due to neurologic dysfunction at lower levels of GFR.

Later Initiation of Dialysis

Patients can be considered for a later initiation of dialysis if they are asymptomatic from a uremic standpoint, have adequate nutritional status, and do not have a decline in either dry weight or serum albumin levels. If renal replacement therapy is delayed, then the patient should be reassessed on a regular basis for a change in these parameters.

Apparatus

The major parts of the dialysis machine are the blood pump, dialyzer, dialysate pump, safety monitors, and alarms (Figure 50–1).

Dialyzer

The artificial kidney or dialyzer consists of the blood compartment, the dialysate compartment, and the semipermeable membrane. The surface area of the dialyzer membrane can be increased by using either parallel plates or hollow fibers. Most dialyzers used in adults have a surface area between 1.5 and 2.1 m2. Parallel plate dialyzers are rarely used today. Most dialysis membranes in use today are made from a variety of synthetic materials including polyamide, polymethylmethacrylate, acrylnitrile-sodium methallylsulfonate (AN-69), polyacrylonitrile, polycarbonate, and polysulfone. Cellulose membranes are being used with decreasing frequency in the United States.

The contact of blood with the membrane can result in activation of the complement system, with the release of bradykinin or cytokines. The biocompatibility of the dialysis membrane depends not only on the material used but also on the degree of blood contact with the dialysate. Unsubstituted cellulose membranes activate the complement system. To decrease complement activation, the hydroxyl groups of cellulose have been replaced with acetate or a synthetic material has been added to cellulose.

Membrane Characteristics and Solute Clearance

A high efficiency membrane has the ability to remove small solutes well. The removal of small solutes is a function of the membrane surface area. High-efficiency membranes have a large surface area. The efficiency of a dialyzer is measured by the clearance of urea (MW 60) and is expressed as KoAurea. Larger molecular-weight solutes are removed to a greater degree by membranes with larger membrane pores. These membranes are referred to as high-flux membranes. High-flux and many high-efficiency membranes also have the ability to achieve a high ultrafiltration rate. The water permeability of a membrane is specified by its ultrafiltration coefficient (Kuf).

The clearance of creatinine (MW 113) by a dialyzer is usually about 20% less than the dialyzer urea clearance, despite the minimal difference in molecular weight. The removal of phosphorus (MW 31) by dialysis depends mostly on the time provided for dialysis per week, and also on the dialyzer efficiency and the predialysis phosphorus level. During dialysis, phosphorus is removed rapidly from plasma but not from the intracellular compartment. The slow equilibration between these compartments and bone is the major limiting factor of phosphorus removal.

Historically, middle molecule clearance was defined by the clearance of vitamin B12 (MW 1355). However, the clearance of vitamin B12 is low due to its high degree of protein binding. Thus, many high-flux dialyzers are now classified based on the clearance of molecules such as β2-microglobulin (MW 11,800). With the introduction of high-flux dialyzers, the clearance of β2-microglobulin has improved. Despite these improvements, the serum concentration of β2-microglobulin remains markedly elevated in anuric hemodialysis patients using high-flux dialyzers. β2-Microglobulin deposition is the cause of dialysis-associated amyloidosis.

Dialyzer Reuse

Reuse of dialyzers is a common practice in outpatient dialysis units in the United States, but is less common in other countries. A method for the reuse process used in the United States has been written by the Association for the Advancement of Medical Instrumentation (AAMI). Each dialyzer should be labeled with the patient's identifying information. The total cell volume (TCV) should be measured prior to its first use. After the dialysis treatment, the membrane is rinsed with normal saline, pressure washed, and then cleansed with either bleach or a hydrogen peroxide mixture. Bleach can damage the membrane and increase protein loss with dialysis if it is used in inappropriately high concentrations. Once the membrane has been cleaned, its performance is evaluated by measuring the TCV. If the new value for TCV is >80% of the original TCV, it passes the performance test, and the membrane can be reused after disinfection and sterilization with a mixture of hydrogen peroxide, formaldehyde, or glutaraldehyde. The polysulfone membranes can also be heat sterilized. The final step of the reuse process is the removal of the germicide. Residual germicide can cause a burning sensation, itching, or other allergic reactions. The reuse of dialyzers needs an informed consent. Patients with bacteremia or hepatitis B are excluded from dialyzer reuse. HIV and hepatitis C infection are not considered contraindications to reuse. In general, membrane biocompatibility improves with dialyzer reuse. Exposure of the membrane to blood can result in the protein coating of the membrane. This protein coating may decrease complement activation. Dialyzers can be reused dozens of times without a significant loss of efficacy. A decrease in the reuse number may suggest an increased rate of clotting of the hollow fibers and can often be improved by adjusting the anticoagulation prescription.

Dialysis Machine

The blood pump moves the blood from the arterial line through the dialyzer back to the venous line. The speed of the blood pump can be adjusted to between 200 and 600 mL/minute. At any given time about 200–250 mL of blood is outside the patient. The dialysis pump sucks the dialysis fluid (dialysate) away from the dialyzer producing the transmembrane pressure. The transmembrane pressure can be adjusted to achieve the desired fluid removal. In modern dialysis machines, the transmembrane pressure is automatically adjusted by the dialysis machine based upon the amount of volume to be removed during the dialysis session and the type of ultrafiltration profiling chosen. The dialysate flow rate is usually between 500 and 800 mL/minute and is usually set between 100 and 200 mL/minute higher than the blood flow rate. The dialysate temperature can be adjusted. A lower temperature can cause peripheral vasoconstriction in the patient and thus improve hemodynamic stability.

The arterial and venous pressures are monitored during the dialysis treatment. The arterial pressure is measured before the blood pump to avoid excessive suction of blood and the venous pressure is measured before the blood returns to the access to avoid excessive resistance. A high venous pressure in the access is suggestive of an impairment to flow in the venous outflow tract that could be due to stenosis in the venous outflow of the access, clotting in the venous chamber of the catheter, stenosis in native vessels through which the access drains, or kinking of the blood lines. A high negative arterial pressure is indicative of immature access, stenosis or scarring in the accessed area, suctioning against the vessel wall, or the use of long or small gauge needles or catheters.

Other safety guards included on dialysis machines are the air trap to detect air embolism, the blood leak detector to detect blood in the dialysate compartment, and the measurement of dialysate conductivity to detect a malfunction in mixing the dialysis solution. If one of these safety guards is triggered, the machine will alarm and in some cases shut down. If a blood leak is detected, the dialyzer will be replaced and the patient will be administered antibiotics to treat any possible contamination of blood with the dialysis solution.

Dialysis Solution

The major electrolyte components of the dialysis solution are sodium, potassium, calcium, magnesium, chloride, bicarbonate, and glucose (Table 50–1). In some dialysis machines, the sodium concentration can be changed during the same treatment (sodium modeling). The concentration of potassium and calcium can be varied to some extent based on the patient's blood chemistries. Calcium and magnesium can react with the bicarbonate in an alkaline environment and precipitate as carbonate salts. These components are stored separately and the final dialysis solution is prepared during the treatment by mixing a concentrated solution of these components with treated water.

Water Treatment

Dialysis water is obtained by processing water from the municipal water supply (Figure 50–2). The water is processed using guidelines developed by the AAMI. With each dialysis treatment over 100 L of water is used to make the dialysis solution. Tap water is contaminated with organic and inorganic compounds, heavy metals and trace elements, bacteria, and endotoxins. In areas in which tap water is hard, a water softener can be used to facilitate calcium and magnesium removal. Organic contaminants such as chloroethylene, benzene, toluene, pesticides, herbicides, chloramine, chlorine, and other halogens are removed by a carbon filter. Chloramine is added by some municipal water agencies to help in the water cleaning process; this agent can cause hemolysis even at very low concentrations. Once the tap water is processed in these preliminary steps, the final processing for removal of contaminants occurs using either reverse osmosis (RO) or deionization. In RO, contaminants are removed by forcing water across a semipermeable membrane using high pressures. RO is very effective in removing bacteria, viruses, pyrogens, and heavy metals such as aluminum. Ultraviolet light can also damage and fragment bacteria. This bacterial debris, however, needs to be removed by the RO system. With deionization, the ionic contaminants are replaced by hydrogen or hydroxyl ions. In addition, various filters can be added to improve water quality. A 5-μm prefilter is used to remove large particles at the beginning of the water treatment system. Fine particles are removed by special filters prior to RO to protect the RO system. In addition, microfilters can be added to enhance the removal of microbial contaminants. Standard quality dialysis fluid is not free from bacteria and endotoxins.

Recently, a trend toward using ultrapure water, especially with use of high-flux dialyzers, has occurred. The term ultrapure water in dialysis refers to pyrogen-free water.

Access

In patients with a GFR less than 30 mL/minute, forearm and arm veins that are suitable for use for a permanent hemodialysis access should not be used for venipuncture, the placement of intravenous catheters, or the placement of subclavian catheters or peripherally inserted central catheter (PICC) lines. Discussions regarding the choice of dialysis modality should begin once the patient's estimated GFR is less than 30 mL/minute. Once the patient chooses hemodialysis as the preferred dialysis modality, a permanent dialysis access should be placed in a timely manner to ensure that this access is functional at the time that the patient initiates chronic hemodialysis therapy. In general, an arteriovenous (AV) fistula should be placed at least 6 months prior to the anticipated start of chronic hemodialysis treatment. This will allow adequate time for any needed revisions to be corrected, eg, arterial stenosis or collateral veins, and still allow adequate time for AV fistula maturation. An AV graft should be placed at least 3–6 weeks prior to the anticipated start of hemodialysis. In addition to a history and physical examination, appropriate preoperative assessment of the patient should include an evaluation of the brachial and radial arteries and peripheral veins of the patient using Doppler ultrasound. In select cases, an evaluation of the central veins should be performed, especially if the patient has had prior internal jugular or subclavian lines.

Type of Dialysis Access

Arteriovenous Fistulas

The AV fistula is the preferred type of chronic hemodialysis vascular access due to a higher primary and secondary patency rate compared to AV grafts. The preferred order of placement for an AV fistula is a wrist (radial-cephalic) primary AV fistula, any other forearm primary AV fistula, an elbow (brachial-cephalic) primary AV fistula, and a transposed brachial basilic vein fistula. This order of placement helps to maximize the number of fistulas that an individual patient can receive. The initial fistulas should be placed in the nondominant arm.

Arteriovenous Grafts

An AV graft should be placed only if an AV fistula cannot be placed due to either small veins or marked obesity of the arm that will render cannulation of an AV fistula difficult due to the depth of the access below the skin.

Catheters and Ports

Uncuffed catheters should be used only in hospitalized patients and only for less than 1 week. A permanent tunneled cuffed catheter or port should be placed as soon as clinically feasible. These tunneled catheters should be placed in the internal jugular vein on the side opposite to an existing or planned AV fistula or graft in order to reduce the risk of central vein stenosis on the side of the permanent access. The position of the tip of the catheter should be verified radiologically. Most uncuffed catheters should have the tip in the superior vena cava. Most cuffed tunneled catheters or ports should have the tip within the right atrium.

Catheters have a high rate of infection, and infection control measures are important to help reduce the rate of infectious complications. Catheters should be examined by trained personnel prior to each dialysis session to assess for possible infection. The catheter dressing should be changed at each dialysis session. The catheter should not be used for any purpose other than dialysis, except in emergencies when no other blood access is available. The use of an antibiotic lock solution may decrease the rate of catheter infections. Catheter lock solutions that can be used include cefazolin (5 mg/mL) with heparin (5000 units/mL) or edetate disodium (EDTA, 30 mg/mL).

Monitoring for Access Dysfunction

Surveillance for access dysfunction on a regular basis may help to improve access patency rates. All permanent accesses should be examined on a regular basis to detect possible stenoses. A high-pitched bruit or an area with a decreased thrill may be suggestive of an area of stenosis and should be evaluated by a fistulogram or other radiologic technique. There are also surveillance techniques that can be used to assess for access dysfunction. Persistent abnormalities in either the physical examination or in the surveillance techniques should result in referral of the patient for a fistulogram or other radiologic procedure.

Arteriovenous Fistulas

Several techniques can be used to assess for access dysfunction in AV fistulas. In order of preference, these include direct flow measurements, recirculation using a non-urea-based method, and duplex Doppler analysis.

Arteriovenous Grafts

Techniques that can be used to assess for access dysfunction in AV grafts, in order of preference, include measurement of intraaccess flow, directly measured static venous pressures, or duplex ultrasound.

Correction of Access Complications

Arteriovenous Fistulas

A patient should have an evaluation of an AV fistula in the presence of inadequate blood flow, hemodynamically significant venous stenosis, aneurysm formation, or ischemia in the access arm. A stenosis is considered to be hemodynamically significant if it is greater than 50% and is accompanied by abnormal physical findings, persistent abnormal surveillance tests, has had a previous thrombosis, or has resulted in an otherwise unexplained decrease in the measured dose of hemodialysis. Hemodynamically significant stenosis should be corrected by either surgical revision or percutaneous transluminal angioplasty. Thrombosis of an AV fistula should be performed as early as possible after the thrombus is detected in order to increase the chances of a successful declotting.

Arteriovenous Grafts

A patient should have revision of an AV graft in the presence of either graft degeneration or pseudoaneurysm formation. If a graft has a 50% or greater stenosis in either the venous outflow tract or the arterial inflow tract, and the stenosis is accompanied by abnormal physical findings, decreased access flow, measured static pressure, or the presence of a past thrombosis, then the stenosis should be treated with either surgical revision or percutaneous transluminal angioplasty. Thrombosis of an AV graft should be done in an expeditious manner to increase the chances of a successful declotting. Thrombus can be treated by surgical thrombectomy, mechanical thrombolysis, or pharmacomechanical thrombolysis. An infected AV graft will need treatment with intravenous antibiotics and it will need to be resected if the infection is extensive.

Catheters and Ports

A catheter or port is considered to be dysfunctional if it is unable to deliver a blood flow rate of at least 300 mL/minute with a prepump arterial pressure of −250 mm Hg. A dysfunctional catheter can be corrected with thrombolytics, endoluminal brush, or if the catheter is incorrectly positioned or of an inadequate length, by catheter replacement. Thrombolytics can be provided using an intraluminal lytic intradialytic lock, an intracatheter thrombolytic infusion, or an interdialytic lock.

The extent of the infection determines how an infected catheter or port should be treated. A catheter exit site infection, in the absence of a tunnel infection, is usually treated with topical antibiotics. All other catheter infections are treated with parenteral antibiotics. The antibiotics used should cover the suspected organisms, which are usually Staphylococcus or Streptococcus. Definitive antibiotic therapy should be chosen based on the organisms isolated by blood culture. The catheter should be removed if the patient does not have an improvement in clinical status in the first 36–48 hours after the initiation of parenteral antibiotic therapy or if the patient is clinically unstable. Catheter salvage can be attempted if the patient is clinical stable. Under these circumstances, the patient should be treated with parenteral antibiotics for 3 weeks and follow-up blood cultures should be obtained 1 week after the completion of a course of antibiotics. Port infections should be treated according to the manufacturer's recommendations.

Assessing the Adequacy of Hemodialysis

Providing a dose of dialysis above a certain minimal level can reduce patient mortality and morbidity. The delivered dose of dialysis should be measured monthly by obtaining a predialysis and postdialysis blood sample for blood urea nitrogen (BUN). It is critical that the post-BUN sample be obtained using a standardized method since recirculation can significantly alter the value of the postdialysis BUN. Both the stop flow or slow flow techniques are acceptable methods for obtaining the postdialysis BUN sample. These samples are then used to calculate the dose of dialysis, expressed as Kt/V, where K is the dialyzer clearance for urea, t is the number of minutes of the treatment, and V is the volume of distribution of urea in the body, approximately equal to total body water.

Minimum Dose of Hemodialysis

Results from multiple clinical trials and observational studies suggest that the minimum dose for three times per week hemodialysis is a Kt/V of at least 1.2. To achieve this delivered dose of dialysis, the prescribed Kt/V should be at least 1.3. For patients receiving hemodialysis on a schedule other than three times per week, the minimum standardized dose of dialysis should be an sKt/V of at least 2.0. This level of sKt/V is equivalent to a single pool Kt/V of 1.2 for patients receiving hemodialysis three times per week.

Preservation of Residual Renal Function

Several studies in the peritoneal dialysis population suggest that residual kidney function is a more important predictor of outcome than peritoneal clearance. Although there are few data on this subject in hemodialysis patients, it is reasonable to assume that preservation of residual kidney function is also beneficial in these patients. Thus, efforts should be taken to preserve residual kidney function in chronic hemodialysis patients, including the avoidance of nephrotoxins, such as contrast dye, nonsteroidal anti-inflammatory drugs (NSAIDs), and aminoglycosides, and the use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (when not contraindicated).

Alternative Hemodialysis Therapies

Alternative schedules for hemodialysis were first developed in the 1960s. Many of the hemodialysis treatments of that era were performed at home, including nocturnal hemodialysis. These home treatments became less popular after Medicare began to cover the costs of performing hemodialysis treatments in an outpatient setting in 1973. In the past 10 years, there has been a renewed interest in both performing hemodialysis at home and performing hemodialysis more than three times per week on a routine basis.

In-Center Hemodialysis Six Times Per Week

Most studies of patients receiving dialysis six times per week (either in-center or at home) have involved small numbers of patients and none includes randomized trials. In general, patients receiving in-center hemodialysis six times per week for less than 4 hours per session report an improvement in quality of life and in control of blood pressure. There does not appear to be an improvement in serum albumin levels, phosphorus levels, or body composition. Some centers have also performed overnight hemodialysis (6–8 hours) three times per week in the dialysis center.

Home Hemodialysis

Home hemodialysis currently accounts for less than 1% of all hemodialysis treatments in the United States. It is more common in other countries such as New Zealand. Home dialysis can be performed during the day or evening 3–6 days per week or overnight for three to six nights per week. Patients receiving home hemodialysis three times per week in the United States have a lower mortality rate and fewer hospitalizations compared to patients receiving in-center hemodialysis; however, it is unclear if these results are due to selection bias, the modality itself, or some combination of the two. Nocturnal home hemodialysis six times per week is performed in small numbers of patients throughout the developed world. Small studies suggest that patients receiving home nocturnal hemodialysis six nights per week have improved blood pressure control, normal phosphorus levels without the use of phosphate binders, and improved levels of physical activity and quality of life.

Hypotension

Hypotension is the most common complication of dialysis. It occurs in up to 30% of hemodialysis treatments. The differential diagnosis is broad. It is often related to an imbalance between fluid removal with dialysis treatment and fluid replacement by the extravascular compartment. During dialysis, fluid is rapidly removed from the intravascular space. The maintenance of blood pressure despite fluid removal is due to a fluid shift from the extravascular space back into the vascular system. A large weight gain between dialysis treatments is a major risk factor for hypotension. This factor is especially important in patients with diabetic neuropathy, low cardiac ejection fraction, and diastolic dysfunction. A low dialysate sodium concentration, elevated dialysate temperature, excessive fluid removal, or intake of antihypertensive medications prior to treatment can also cause hypotension during dialysis. Patients are advised to limit their food intake prior to or during the dialysis treatment to avoid splanchnic vasodilation and hypotension. If dialysis access is provided by a catheter, bacteremia and early sepsis syndrome need to be considered and empiric antibiotic coverage initiated. Arrhythmias, pericardiac tamponade, sepsis, hemolysis, dialyzer reactions, bleeding, and air embolus are other possible causes of hypotension. Hypotension can result in cardiac ischemia and loss of access secondary to access thrombosis.

If a patient becomes hypotensive during hemodialysis, the ultrafiltration is stopped and the blood flow is decreased. If the patient remains hypotensive, normal saline and occasionally albumin can be infused. To prevent hypotension, intradialytic weight gain has to be limited by minimizing the fluid intake and avoiding salt intake. If the patient is anemic this needs to be corrected. Starting the dialysis with a higher sodium concentration and gradually decreasing the sodium concentration during dialysis (sodium modeling) have been reported to improve hemodynamic stability. However, sodium modeling has been linked to increased intradialytic weight gain and thirst. Increasing the dialysate calcium also improves hemodynamic stability. Lowering the dialysate temperature is also beneficial if it is acceptable to the patient. Recently, midodrine has been used to improve peripheral vasoconstriction in patients who are either not responsive to the above measures or who have autonomic dysfunction. Midodrine is a selective α1-agonist that is given 1 hour before the initiation of dialysis. The dose can be repeated 1 hour into dialysis. Its use is contraindicated in patients with heart disease, urinary retention, and thyrotoxicosis.

Muscle Cramps

Muscle cramps are believed to be related to shifts in fluids and electrolytes. It is an early sign of ultrafiltration down to the patient's dry weight. Quinine is often used off-label for the treatment of leg cramps. Vitamin E intake might also be beneficial for this condition. Infusion of a hypertonic glucose solution (50 mL of 50% dextrose) can provide acute relief.

Nausea and Vomiting

Nausea and vomiting are common symptoms, especially during the first hour of dialysis. It is usually associated with hypotension and responds to the treatment of hypotension. It can also be an early symptom of the dysequilibrium syndrome, dialyzer reaction, cardiac or intestinal ischemia, or hypercalcemia. The differential diagnosis is broad and includes reflux disease, gastroparesis, peptic ulcer disease, and gastroenteritis. The treatment is symptomatic.