Hemodialysis relies on the principles of solute diffusion across a semipermeable membrane. Movement of metabolic waste products takes place down a concentration gradient from the circulation into the dialysate. The rate of diffusive transport increases in response to several factors, including the magnitude of the concentration gradient, the membrane surface area, and the mass transfer coefficient of the membrane. The latter is a function of the porosity and thickness of the membrane, the size of the solute molecule, and the conditions of flow on the two sides of the membrane. According to laws of diffusion, the larger the molecule, the slower is its rate of transfer across the membrane. A small molecule, such as urea (60 Da), undergoes substantial clearance, whereas a larger molecule, such as creatinine (113 Da), is cleared less efficiently. In addition to diffusive clearance, movement of waste products from the circulation into the dialysate may occur as a result of ultrafiltration. Convective clearance occurs because of solvent drag, with solutes being swept along with water across the semipermeable dialysis membrane.
There are three essential components to hemodialysis: the dialyzer, the composition and delivery of the dialysate, and the blood delivery system (Fig. 336-1). The dialyzer is a plastic chamber with the ability to perfuse blood and dialysate compartments simultaneously at very high flow rates. The hollow-fiber dialyzer is the most common in use in the United States. These dialyzers are composed of bundles of capillary tubes through which blood circulates while dialysate travels on the outside of the fiber bundle. The majority of dialyzers now manufactured in the United States are “biocompatible” synthetic membranes derived from polysulfone or related compounds (versus older cellulose “bioincompatible” membranes that activated the complement cascade). The frequency of reprocessing and reuse of hemodialyzers and blood lines varies across the world. In general, as the cost of disposable supplies has decreased, their use has increased. Formaldehyde, peracetic acid–hydrogen peroxide, glutaraldehyde, and bleach have all been used as reprocessing agents.
Schema for hemodialysis. A, artery; V, vein.
The potassium concentration of dialysate may be varied from 0 to 4 mmol/L depending on the predialysis serum potassium concentration. The usual dialysate calcium concentration is 1.25 mmol/L (2.5 meq/L), although modification may be required in selected settings (e.g., higher dialysate calcium concentrations may be used in patients with hypocalcemia associated with secondary hyperparathyroidism or following parathyroidectomy). The usual dialysate sodium concentration is 136–140 mmol/L. In patients who frequently develop hypotension during their dialysis run, “sodium modeling” to counterbalance urea-related osmolar gradients is often used. With sodium modeling, the dialysate sodium concentration is gradually lowered from the range of 145–155 mmol/L to isotonic concentrations (136–140 mmol/L) near the end of the dialysis treatment, typically declining either in steps or in a linear or exponential fashion. Higher dialysate sodium concentrations and sodium modeling may predispose patients to positive sodium balance and increased thirst; thus, these strategies to ameliorate intradialytic hypotension may be undesirable in hypertensive patients or in patients with large interdialytic weight gains. Because patients are exposed to approximately 120 L of water during each dialysis treatment, water used for the dialysate is subjected to filtration, softening, deionization, and, ultimately, reverse osmosis to remove microbiologic contaminants and dissolved ions.
The blood delivery system is composed of the extracorporeal circuit and the dialysis access. The dialysis machine consists of a blood pump, dialysis solution delivery system, and various safety monitors. The blood pump moves blood from the access site, through the dialyzer, and back to the patient. The blood flow rate may range from 250–500 mL/min, depending on the type and integrity of the vascular access. Negative hydrostatic pressure on the dialysate side can be manipulated to achieve desirable fluid removal or ultrafiltration. Dialysis membranes have different ultrafiltration coefficients (i.e., mL removed/min per mmHg) so that along with hydrostatic changes, fluid removal can be varied. The dialysis solution delivery system dilutes the concentrated dialysate with water and monitors the temperature, conductivity, and flow of dialysate.
The fistula, graft, or catheter through which blood is obtained for hemodialysis is often referred to as a dialysis access. A native fistula created by the anastomosis of an artery to a vein (e.g., the Brescia-Cimino fistula, in which the cephalic vein is anastomosed end-to-side to the radial artery) results in arterialization of the vein. This facilitates its subsequent use in the placement of large needles (typically 15 gauge) to access the circulation. Although fistulas have the highest long-term patency rate of all dialysis access options, fistulas are created in a minority of patients in the United States. Many patients undergo placement of an arteriovenous graft (i.e., the interposition of prosthetic material, usually polytetrafluoroethylene, between an artery and a vein) or a tunneled dialysis catheter. In recent years, nephrologists, vascular surgeons, and health care policy makers in the United States have encouraged creation of arteriovenous fistulas in a larger fraction of patients (the “fistula first” initiative). Unfortunately, even when created, arteriovenous fistulas may not mature sufficiently to provide reliable access to the circulation, or they may thrombose early in their development.
Grafts and catheters tend to be used among persons with smaller-caliber veins or persons whose veins have been damaged by repeated venipuncture, or after prolonged hospitalization. The most important complication of arteriovenous grafts is thrombosis of the graft and graft failure, due principally to intimal hyperplasia at the anastomosis between the graft and recipient vein. When grafts (or fistulas) fail, catheter-guided angioplasty can be used to dilate stenoses; monitoring of venous pressures on dialysis and of access flow, although not routinely performed, may assist in the early recognition of impending vascular access failure. In addition to an increased rate of access failure, grafts and (in particular) catheters are associated with much higher rates of infection than fistulas.
Intravenous large-bore catheters are often used in patients with acute and chronic kidney disease. For persons on maintenance hemodialysis, tunneled catheters (either two separate catheters or a single catheter with two lumens) are often used when arteriovenous fistulas and grafts have failed or are not feasible due to anatomic considerations. These catheters are tunneled under the skin; the tunnel reduces bacterial translocation from the skin, resulting in a lower infection rate than with nontunneled temporary catheters. Most tunneled catheters are placed in the internal jugular veins; the external jugular, femoral, and subclavian veins may also be used.
Nephrologists, interventional radiologists, and vascular surgeons generally prefer to avoid placement of catheters into the subclavian veins; while flow rates are usually excellent, subclavian stenosis is a frequent complication and, if present, will likely prohibit permanent vascular access (i.e., a fistula or graft) in the ipsilateral extremity. Infection rates may be higher with femoral catheters. For patients with multiple vascular access complications and no other options for permanent vascular access, tunneled catheters may be the last “lifeline” for hemodialysis. Translumbar or transhepatic approaches into the inferior vena cava may be required if the superior vena cava or other central veins draining the upper extremities are stenosed or thrombosed.
The hemodialysis procedure consists of pumping heparinized blood through the dialyzer at a flow rate of 300–500 mL/min, while dialysate flows in an opposite counter-current direction at 500–800 mL/min. The efficiency of dialysis is determined by blood and dialysate flow through the dialyzer as well as dialyzer characteristics (i.e., its efficiency in removing solute). The dose of dialysis, which is currently defined as a derivation of the fractional urea clearance during a single treatment, is further governed by patient size, residual kidney function, dietary protein intake, the degree of anabolism or catabolism, and the presence of comorbid conditions.
Since the landmark studies of Sargent and Gotch relating the measurement of the dose of dialysis using urea concentrations with morbidity in the National Cooperative Dialysis Study, the delivered dose of dialysis has been measured and considered as a quality assurance and improvement tool. Although the fractional removal of urea nitrogen and derivations thereof are considered to be the standard methods by which “adequacy of dialysis” is measured, a large multicenter randomized clinical trial (the HEMO Study) failed to show a difference in mortality associated with a large difference in urea clearance. Current targets include a urea reduction ratio (the fractional reduction in blood urea nitrogen per hemodialysis session) of >65–70% and a body water–indexed clearance × time product (KT/V) above 1.2 or 1.05, depending on whether urea concentrations are “equilibrated.” For the majority of patients with ESRD, between 9 and 12 h of dialysis are required each week, usually divided into three equal sessions. Several studies have suggested that longer hemodialysis session lengths may be beneficial (independent of urea clearance), although these studies are confounded by a variety of patient characteristics, including body size and nutritional status. Hemodialysis “dose” should be individualized, and factors other than the urea nitrogen should be considered, including the adequacy of ultrafiltration or fluid removal and control of hyperkalemia, hyperphosphatemia, and metabolic acidosis. A recent randomized clinical trial (the Frequent Hemodialysis Network Trial) demonstrated improved control of hypertension and hyperphosphatemia, reduced left ventricular mass, and improved self-reported physical health with six times per week hemodialysis compared to the usual three times per week therapy. A companion trial in which frequent nocturnal hemodialysis was compared to conventional hemodialysis at home showed no significant effect on left ventricular mass or self-reported physical health. Finally, an evaluation of the U.S. Renal Data System registry showed a significant increase in mortality and hospitalization for heart failure after the longer interdialytic interval that occurs over the dialysis “weekend.”
COMPLICATIONS DURING HEMODIALYSIS
Hypotension is the most common acute complication of hemodialysis, particularly among patients with diabetes mellitus. Numerous factors appear to increase the risk of hypotension, including excessive ultrafiltration with inadequate compensatory vascular filling, impaired vasoactive or autonomic responses, osmolar shifts, overzealous use of antihypertensive agents, and reduced cardiac reserve. Patients with arteriovenous fistulas and grafts may develop high-output cardiac failure due to shunting of blood through the dialysis access; on rare occasions, this may necessitate ligation of the fistula or graft. Because of the vasodilatory and cardiodepressive effects of acetate, its use as the buffer in dialysate was once a common cause of hypotension. Since the introduction of bicarbonate-containing dialysate, dialysis-associated hypotension has become less common. The management of hypotension during dialysis consists of discontinuing ultrafiltration, the administration of 100–250 mL of isotonic saline or 10 mL of 23% saturated hypertonic saline, or administration of salt-poor albumin. Hypotension during dialysis can frequently be prevented by careful evaluation of the dry weight and by ultrafiltration modeling, such that more fluid is removed at the beginning rather than the end of the dialysis procedure. Additional maneuvers include the performance of sequential ultrafiltration followed by dialysis, cooling of the dialysate during dialysis treatment, and avoiding heavy meals during dialysis. Midodrine, an oral selective α1 adrenergic agent, has been advocated by some practitioners, although there is insufficient evidence of its safety and efficacy to support its routine use.
Muscle cramps during dialysis are also a common complication. The etiology of dialysis-associated cramps remains obscure. Changes in muscle perfusion because of excessively rapid volume removal (e.g., >10–12 mL/kg per hour) or targeted removal below the patient’s estimated dry weight often precipitate dialysis-associated cramps. Strategies that may be used to prevent cramps include reducing volume removal during dialysis, ultrafiltration profiling, and the use of sodium modeling (see above).
Anaphylactoid reactions to the dialyzer, particularly on its first use, have been reported most frequently with the bioincompatible cellulosic-containing membranes. Dialyzer reactions can be divided into two types, A and B. Type A reactions are attributed to an IgE-mediated intermediate hypersensitivity reaction to ethylene oxide used in the sterilization of new dialyzers. This reaction typically occurs soon after the initiation of a treatment (within the first few minutes) and can progress to full-blown anaphylaxis if the therapy is not promptly discontinued. Treatment with steroids or epinephrine may be needed if symptoms are severe. The type B reaction consists of a symptom complex of nonspecific chest and back pain, which appears to result from complement activation and cytokine release. These symptoms typically occur several minutes into the dialysis run and typically resolve over time with continued dialysis.