In medicine,�dialysis is primarily used to provide an artificial replacement for lost kidney function (renal replacement therapy) due to renal failure. Dialysis may be used for very sick patients who have suddenly but temporarily, lost their kidney function (acute renal failure) or for quite stable patients who have permanently lost their kidney function (stage 5 chronic kidney disease). For patients with stage 5, or End-Stage Kidney Disease (ESKD), the decline in kidney function occurred over a period of months to years until a level was reached at which treatment was needed for survival. Unlike Acute Renal Failure (ARF) (Acute Kidney Injury (AKI)), Chronic Kidney Failure cannot be cured or reversed and long-term treatments are needed to replace the lost functions of the kidney. The treatment for ESKD that most naturally replaces lost kidney function is a�kidney transplant. However, some patients are not good candidates for a transplant due to medical or other reasons, some cannot receive a transplant because of the short supply of donor kidneys, and others simply decide that a transplant is not the best option for them. As a result, most patients with ESKD must rely on dialysis to replace the water and waste removal functions of the healthy kidneys.
PrincipleDialysis works on the principles of the diffusion of solutes and ultrafiltration of fluid across a�semi-permeable membrane. Diffusion describes a property of substances in water. Substances in water tend to move from an area where they are in a high concentration to an area of low concentration. Blood flows by one side of a semi-permeable membrane, and a dialysate, or special dialysis fluid, flows by the opposite side. A semipermeable membrane is a thin layer of material that contains various sized holes, or pores. Smaller solutes and fluid pass through the membrane, but the membrane blocks the passage of larger substances (for example, red blood cells, large proteins). The two main types of dialysis, Hemodialysis (HD) and Peritoneal dialysis (PD), remove wastes and excess water from the blood in different ways. Hemodialysis removes wastes and water by circulating blood outside the body through an external filter, called a dialyzer, that contains a semipermeable membrane. The blood flows in one direction and the dialysate flows in the opposite. The counter-current flow of the blood and dialysate maximizes the concentration gradient of solutes between the blood and dialysate, which helps to remove more urea and creatinine from the blood. The concentrations of solutes (for example potassium, phosphorus, and urea) are undesirably high in the blood, but low or absent in the dialysis solution and constant replacement of the dialysate ensures that the concentration of undesired solutes is kept low on this side of the membrane. The dialysis solution has levels of minerals like potassium and calcium that are similar to their natural concentration in healthy blood. For another solute, bicarbonate, dialysis solution level is set at a slightly higher level than in normal blood, to encourage diffusion of bicarbonate into the blood, to act as a pH buffer to neutralize the metabolic acidosis that is often present in these patients. The levels of the components of dialysate are typically prescribed by a nephrologist according to the needs of the individual patient. In peritoneal dialysis, wastes and water are removed from the blood inside the body using the peritoneal membrane as a natural semipermeable membrane. Wastes and excess water move from the blood, across the peritoneal membrane, and into a special dialysis solution, called dialysate, in the abdominal cavity which has a composition similar to the fluid portion of blood.
TypesThere are two primary types of dialysis, hemodialysis and peritoneal dialysis, and a third investigational type, intestinal dialysis.
HemodialysisIn hemodialysis, the patient`s blood is pumped through the blood compartment of a dialyzer, exposing it to a partially permeable membrane. The dialyzer is composed of thousands of tiny synthetic hollow fibers. The fiber wall acts as the semipermeable membrane. Blood flows through the fibers, dialysis solution flows around the outside the fibers, and water and wastes move between these two solutions.� The cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane. This usually is done by applying a negative pressure to the dialysate compartment of the dialyzer. This pressure gradient causes water and dissolved solutes to move from blood to dialysate, and allows the removal of several litres of excess fluid during a typical 3 to 5 hour treatment. In the US, hemodialysis treatments are typically given in a dialysis center three times per week (due in the US to Medicare reimbursement rules); however, as of 2007 over 2,500 people in the US are dialyzing at home more frequently for various treatment lengths. Studies have demonstrated the clinical benefits of dialyzing 5 to 7 times a week, for 6 to 8 hours. These frequent long treatments are often done at home, while sleeping but home dialysis is a flexible modality and schedules can be changed day to day, week to week. In general, studies have shown that both increased treatment length and frequency are clinically beneficial.
In peritoneal dialysis, a sterile solution containing minerals and glucose is run through a tube into the peritoneal cavity, the abdominal body cavity around the intestine, where the peritoneal membrane acts as a semipermeable membrane.The peritoneal membrane or peritoneum is a layer of tissue containing blood vessels that lines and surrounds the peritoneal, or abdominal, cavity and the internal abdominal organs (stomach, spleen, liver, and intestines).� The dialysate is left there for a period of time to absorb waste products, and then it is drained out through the tube and discarded. This cycle or �exchange� is normally repeated 4-5 times during the day, (sometimes more often overnight with an automated system). Ultrafiltration occurs via osmosis; the dialysis solution used contains a high concentration of glucose, and the resulting osmotic pressure causes fluid to move from the blood into the dialysate. As a result, more fluid is drained than was instilled. Peritoneal dialysis is less efficient than hemodialysis, but because it is carried out for a longer period of time the net effect in terms of removal of waste products and of salt and water are similar to hemodialysis. Peritoneal dialysis is carried out at home by the patient. Although support is helpful, it is not essential. It does free patients from the routine of having to go to a dialysis clinic on a fixed schedule multiple times per week, and it can be done while travelling with a minimum of specialized equipment.
HemofiltrationHemofiltration is a similar treatment to hemodialysis, but it makes use of a different principle. The blood is pumped through a dialyzer or �hemofilter� as in dialysis, but no dialysate is used. A pressure gradient is applied; as a result, water moves across the very permeable membrane rapidly, �dragging� along with it many dissolved substances, importantly ones with large molecular weights, which are cleared less well by hemodialysis. Salts and water lost from the blood during this process are replaced with a �substitution fluid� that is infused into the extracorporeal circuit during the treatment.�Hemodiafiltration�is a term used to describe several methods of combining hemodialysis and hemofiltration in one process.
Intestinal dialysisIn intestinal dialysis, the diet is supplemented with soluble fibres such as acacia fibre, which is digested by bacteria in the colon. This bacterial growth increases the amount of nitrogen that is eliminated in fecal waste.  An alternative approach utilizes the ingestion of 1 to 1.5 liters of non-absorbable solutions of polyethylene glycol or mannitol every fourth hour.
Starting indicationsThe decision to initiate dialysis or hemofiltration in patients with renal failure depends on several factors. These can be divided into acute or chronic indications.
HemodialysisIn medicine,�hemodialysis (also�haemodialysis) is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies (the other two being renal transplant; peritoneal dialysis). Hemodialysis can be an outpatient or inpatient therapy. Routine hemodialysis is conducted in a dialysis outpatient facility, either a purpose built room in a hospital or a dedicated, stand alone clinic. Less frequently hemodialysis is done at home. Dialysis treatments in a clinic are initiated and managed by specialized staff made up of nurses and technicians; dialysis treatments at home can be self initiated and managed or done jointly with the assistance of a trained helper who is usually a family member.
PrincipleThe principle of hemodialysis is the same as other methods of dialysis; it involves diffusion of solutes across a semipermeable membrane. Hemodialysis utilizes counter current flow, where the dialysate is flowing in the opposite direction to blood flow in the extracorporeal circuit. Counter-current flow maintains the concentration gradient across the membrane at a maximum and increases the efficiency of the dialysis. Fluid removal (ultrafiltration) is achieved by altering the hydrostatic pressure of the dialysate compartment, causing free water and some dissolved solutes to move across the membrane along a created pressure gradient. The dialysis solution that is used is a sterilized solution of mineral ions. Urea and other waste products, potassium, and phosphate diffuse into the dialysis solution. However, concentrations of sodium and chloride are similar to those of normal plasma to prevent loss. Sodium bicarbonate is added in a higher concentration than plasma to correct blood acidity. A small amount of glucose is also commonly used. Note that this is a different process to the related technique of hemofiltration.
 HistoryMany have played a role in developing dialysis as a practical treatment for renal failure, starting with Thomas Graham of Glasgow, who first presented the principles of solute transport across a semipermeable membrane in 1854. The artificial kidney was first developed by Abel, Rountree and Turner in 1913,, the first hemodialysis in a human being was by Hass (February 28, 1924) and the artificial kidney was developed into a clinically useful apparatus by Kolff in 1943 � 1945. This research showed that life could be prolonged in patients dying of renal failure. Dr.�Willem Kolff was the first to construct a working dialyzer in 1943. The first successfully treated patient was a 67-year-old woman in uremic coma who regained consciousness after 11 hours of hemodialysis with Kolff�s dialyzer in 1945. At the time of its creation, Kolff�s goal was to provide life support during recovery from acute renal failure. After World War II ended, Kolff donated the five dialyzers he had made to hospitals around the world, including Mount Sinai Hospital, New York. Kolff gave a set of blueprints for his hemodialysis machine to George Thorn at the Peter Bent Brigham Hospital in Boston. This led to the manufacture of the next generation of Kolff�s dialyzer, a stainless steel Kolff-Brigham dialysis machine. By the 1950s, Willem Kolff�s invention of the dialyzer was used for acute renal failure, but it was not seen as a viable treatment for patients with stage 5 chronic kidney disease (CKD). At the time, doctors believed it was impossible for patients to have dialysis indefinitely for two reasons. First, they thought no man-made device could replace the function of kidneys over the long term. In addition, a patient undergoing dialysis suffered from damaged veins and arteries, so that after several treatments, it became difficult to find a vessel to access the patient�s blood. Dr. Nils Alwall: The original Kolff kidney was not very useful clinically, because it did not allow for removal of excess fluid. Dr. Nils Alwall� encased a modified version of this kidney inside a stainless steel canister, to which a negative pressure could be applied, in this way effecting the first truly practical application of hemodialysis, which was done in 1946 at the University of Lund. Alwall also was arguably the inventor of the arteriovenous shunt for dialysis. He reported this first in 1948 where he used such an arteriovenous shunt in rabbits. Subsequently he used such shunts, made of glass, as well as his canister-enclosed dialyzer, to treat 1500 patients in renal failure between 1946 and 1960, as reported to the First International Congress of Nephrology held in Evian in September 1960. Alwall was appointed to a newly-created Chair of Nephrology at the University of Lund in 1957. Subsequently, he collaborated with Swedish businessman Holger Crafoord to found one of the key companies that would manufacture dialysis equipment in the past 50 years, Gambro, Inc. The early history of dialysis has been reviewed by Stanley Shaldon Dr.�Belding H. Scribner working with a surgeon, Dr. Wayne Quinton, modified the glass shunts used by Alwall by making them from Teflon. Another key improvement was to connect them to a short piece of silicone elastomer tubing. This formed the basis of the so-called Scribner shunt, perhaps more properly called the Quinton-Scribner shunt. After treatment, the circulatory access would be kept open by connecting the two tubes outside the body using a small U-shaped Teflon tube, which would shunt the blood from the tube in the artery back to the tube in the vein In 1962, Scribner started the world�s first outpatient dialysis facility, the Seattle Artificial Kidney Center, later renamed the Northwest Kidney Centers. Immediately the problem arose of who should be given dialysis, since demand far exceeded the capacity of the six dialysis machines at the center. Scribner decided that the decision about who would receive dialysis and who wouldn�t, would not be made by him. Instead, the choices would be made by an anonymous committee, which could be viewed as one of the first bioethics committees. For a detailed history of successful and unsuccessful attempts at dialysis, including pioneers such as Abel and Roundtree, Haas, and Necheles, see this review by Kjellstrand
PrescriptionA prescription for dialysis by a nephrologist (a medical kidney specialist) will specify various parameters for a dialysis treatment. These include frequency (how many treatments per week), length of each treatment, and the blood and dialysis solution flow rates, as well as the size of the dialyzer. The composition of the dialysis solution is also sometimes adjusted in terms of its sodium and potassium and bicarbonate levels. In general, the larger the body size of an individual, the more dialysis he/she will need. In the North America and UK, 3-4 hour treatments (sometimes up to 5 hours for larger patients) given 3 times a week are typical. Twice-a-week sessions are limited to patients who have a substantial residual kidney function. Four sessions per week are often prescribed for larger patients, as well as patients who have trouble with fluid overload. Finally, there is growing interest in short daily home hemodialysis, which is 1.5 � 4 hr sessions given 5-7 times per week, usually at home. There also is interest in nocturnal dialysis, which involves dialyzing a patient, usually at home, for 8�10 hours per night, 3-6 nights per week. Nocturnal in-center dialysis, 3-4 times per week is also offered at a handful of dialysis units in the United States.
Side effects and complicationsHemodialysis often involves fluid removal (through ultrafiltration), because most patients with renal failure pass little or no urine. Side effects caused by removing too much fluid and/or removing fluid too rapidly include low blood pressure, fatigue, chest pains, leg-cramps, nausea and headaches. These symptoms can occur during the treatment and can persist post treatment; they are sometimes collectively referred to as the dialysis hangover or dialysis washout. The severity of these symptoms is usually proportionate to the amount and speed of fluid removal. However, the impact of a given amount or rate of fluid removal can vary greatly from person to person and day to day. These side effects can be avoided and/or their severity lessened by limiting fluid intake between treatments or increasing the dose of dialysis e.g. dialyzing more often or longer per treatment than the standard three times a week, 3�4 hours per treatment schedule. Since hemodialysis requires access to the circulatory system, patients undergoing hemodialysis may expose their circulatory system to microbes, which can lead to sepsis, an infection affecting the heart valves (endocarditis) or an infection affecting the bones (osteomyelitis). The risk of infection varies depending on the type of access used (see below). Bleeding may also occur, again the risk varies depending on the type of access used. Infections can be minimized by strictly adhering to infection control best practices. Heparin is the most commonly used anticoagulant in hemodialysis, as it is generally well tolerated and can be quickly reversed with protamine sulfate. Heparin allergy can infrequently be a problem and can cause a low platelet count. In such patients, alternative anticoagulants can be used. In patients at high risk of bleeding, dialysis can be done without anticoagulation. First Use Syndrome is a rare but severe anaphylactic reaction to the artificial kidney. Its symptoms include sneezing, wheezing, shortness of breath, back pain, chest pain, or sudden death. It can be caused by residual sterilant in the artificial kidney or the material of the membrane itself. In recent years, the incidence of First Use Syndrome has decreased, due to an increased use of gamma irradiation, steam sterilization, or electron-beam radiation instead of chemical sterilants, and the development of new semipermeable membranes of higher biocompatibility. New methods of processing previously acceptable components of dialysis must always been considered. For example, in 2008, a series of first-use type or reactions, including deaths occurred due to heparin contaminated during the manufacturing process with oversulfated chondroitin sulfate. Longterm complications of hemodialysis include amyloidosis, neuropathy and various forms of heart disease. Increasing the frequency and length of treatments have been shown to improve fluid overload and enlargement of the heart that is commonly seen in such patients. Listed below are specific complications associated with different types of hemodialysis access.
AccessIn hemodialysis, three primary methods are used to gain access to the blood: an intravenous catheter, an arteriovenous (AV) fistula and a synthetic graft. The type of access is influenced by factors such as the expected time course of a patient`s renal failure and the condition of his or her vasculature. Patients may have multiple accesses, usually because an AV fistula or graft is maturing and a catheter is still being used.
CatheterCatheter access, sometimes called a CVC (Central Venous Catheter), consists of a plastic catheter with two lumens (or occasionally two separate catheters) which is inserted into a large vein (usually the vena cava, via the internal jugular vein or the femoral vein) to allow large flows of blood to be withdrawn from one lumen, to enter the dialysis circuit, and to be returned via the other lumen. However, blood flow is almost always less than that of a well functioning fistula or graft. Catheters are usually found in two general varieties, tunnelled and non-tunnelled. Non-tunnelled catheter access is for short-term access (up to about 10 days, but often for one dialysis session only), and the catheter emerges from the skin at the site of entry into the vein. Tunnelled catheter access involves a longer catheter, which is tunnelled under the skin from the point of insertion in the vein to an exit site some distance away. It is usually placed in the internal jugular vein in the neck and the exit site is usually on the chest wall. The tunnel acts as a barrier to invading microbes, and as such, tunnelled catheters are designed for short- to medium-term access (weeks to months only), because infection is still a frequent problem. Aside from infection, venous stenosis is another serious problem with catheter access. The catheter is a foreign body in the vein and often provokes an inflammatory reaction in the vein wall. This results in scarring and narrowing of the vein, often to the point of occlusion. This can cause problems with severe venous congestion in the area drained by the vein and may also render the vein, and the veins drained by it, useless for creating a fistula or graft at a later date. Patients on long-term hemodialysis can literally `run out` of access, so this can be a fatal problem. Catheter access is usually used for rapid access for immediate dialysis, for tunnelled access in patients who are deemed likely to recover from acute renal failure, and for patients with end-stage renal failure who are either waiting for alternative access to mature or who are unable to have alternative access. Catheter access is often popular with patients, because attachment to the dialysis machine doesn`t require needles. However, the serious risks of catheter access noted above mean that such access should be contemplated only as a long-term solution in the most desperate access situation.
AV fistula.AV (arteriovenous) fistulas are recognized as the preferred access method. To create a fistula, a vascular surgeon joins an artery and a vein together through anastomosis. Since this bypasses the capillaries, blood flows rapidly through the fistula. One can feel this by placing one`s finger over a mature fistula. This is called feeling for �thrill� and produces a distinct `buzzing` feeling over the fistula. One can also listen through a stethoscope for the sound of the blood �whooshing� through the fistula, a sound called�bruit. Fistulas are usually created in the nondominant arm and may be situated on the hand (the `snuffbox` fistula`), the forearm (usually a�radiocephalic fistula, or so-called Brescia-Cimino fistula, in which the radial artery is anastomosed to the cephalic vein), or the elbow (usually a brachiocephalic fistula, where the brachial artery is anastomosed to the cephalic vein). A fistula will take a number of weeks to mature, on average perhaps 4�6 weeks. During treatment, two needles are inserted into the fistula, one to draw blood and one to return it. The advantages of the AV fistula use are lower infection rates, because no foreign material is involved in their formation, higher blood flow rates (which translates to more effective dialysis), and a lower incidence of thrombosis. The complications are few, but if a fistula has a very high blood flow and the vasculature that supplies the rest of the limb is poor, a steal syndrome can occur, where blood entering the limb is drawn into the fistula and returned to the general circulation without entering the limb`s capillaries. This results in cold extremities of that limb, cramping pains, and, if severe, tissue damage. One long-term complication of an AV fistula can be the development of an aneurysm, a bulging in the wall of the vein where it is weakened by the repeated insertion of needles over time. To a large extent the risk of developing an aneurysm can be reduced by careful needling technique. Aneurysms may necessitate corrective surgery and may shorten the useful life of a fistula. To prevent damage to the fistula and aneurysm or pseudoaneurysm formation, it is recommended that the needle be inserted at different points in a rotating fashion. Another approach is to cannulate the fistula with a blunted needle, in exactly the same place. This is called a `buttonhole` approach. Often two or three buttonhole places are available on a given fistula. This also can prolong fistula life and help prevent damage to the fistula.
AV graftAV (arteriovenous) grafts are much like fistulas in most respects, except that an artificial vessel is used to join the artery and vein. The graft usually is made of a synthetic material, often PTFE, but sometimes chemically treated, sterilized veins from animals are used. Grafts are inserted when the patient`s native vasculature does not permit a fistula. They mature faster than fistulas, and may be ready for use several weeks after formation (some newer grafts may be used even sooner). However, AV grafts are at high risk to develop narrowing, especially in the vein just downstream from where the graft has been sewn to the vein. Narrowing often leads to clotting or thrombosis. As foreign material, they are at greater risk for becoming infected. More options for sites to place a graft are available, because the graft can be made quite long. Thus a graft can be placed in the thigh or even the neck (the `necklace graft`).
Fistula First projectAV fistulas have a much better access patency and survival than do venous catheters or grafts. They also produce better patient survival and have far fewer complications compared to grafts or venous catheters. For this reason, the Centers for Medicare & Medicaid (CMS) has set up a Fistula First Initiative , whose goal is to increase the use of AV fistulas in dialysis patients.
EquipmentThe hemodialysis machine pumps the patient`s blood and the dialysate through the dialyzer. The newest dialysis machines on the market are highly computerized and continuously monitor an array of safety-critical parameters, including blood and dialysate flow rates; dialysis solution conductivity, temperature, and pH; and analysis of the dialysate for evidence of blood leakage or presence of air. Any reading that is out of normal range triggers an audible alarm to alert the patient-care technician who is monitoring the patient. Manufacturers of dialysis machines include companies such as Fresenius, Gambro, Baxter, B. Braun, NxStage and Bellco.
Water systemAn extensive water purification system is absolutely critical for hemodialysis. Since dialysis patients are exposed to vast quantities of water, which is mixed with dialysate concentrate to form the dialysate, even trace mineral contaminants or bacterial endotoxins can filter into the patient`s blood. Because the damaged kidneys cannot perform their intended function of removing impurities, ions introduced into the bloodstream via water can build up to hazardous levels, causing numerous symptoms or death. Aluminum, chloramine, fluoride, copper, and zinc, as well as bacterial fragments and endotoxins, have all caused problems in this regard. For this reason, water used in hemodialysis is carefully purified before use. Initially it is filtered and temperature-adjusted and its pH is corrected by adding an acid or base. Then it is softened. Next the water is run through a tank containing activated charcoal to adsorb organic contaminants. Primary purification is then done by forcing water through a membrane with very tiny pores, a so-called reverse osmosis membrane. This lets the water pass, but holds back even very small solutes such as electrolytes. Final removal of leftover electrolytes is done by passing the water through a tank with ion-exchange resins, which remove any leftover anions or cations and replace them with hydroxyl and hydrogen molecules, respectively, leaving ultrapure water. Even this degree of water purification may be insufficient. The trend lately is to pass this final purified water (after mixing with dialysate concentrate) through a dialyzer membrane. This provides another layer of protection by removing impurities, especially those of bacterial origin, that may have accumulated in the water after its passage through the original water purification system. Once purified water is mixed with dialysate concentrate, its conductivity increases, since water that contains charged ions conducts electricity. During dialysis, the conductivity of dialysis solution is continuously monitored to ensure that the water and dialysate concentrate are being mixed in the proper proportions. Both excessively concentrated dialysis solution and excessively dilute solution can cause severe clinical problems.
DialyzerThe dialyzer is the piece of equipment that actually filters the blood. Almost all dialyzers in use today are of the hollow-fiber variety. A cylindrical bundle of hollow fibers, whose walls are composed of semi-permeable membrane, is anchored at each end into potting compound (a sort of glue). This assembly is then put into a clear plastic cylindrical shell with four openings. One opening or blood port at each end of the cylinder communicates with each end of the bundle of hollow fibers. This forms the �blood compartment� of the dialyzer. Two other ports are cut into the side of the cylinder. These communicate with the space around the hollow fibers, the �dialysate compartment.� Blood is pumped via the blood ports through this bundle of very thin capillary-like tubes, and the dialysate is pumped through the space surrounding the fibers. Pressure gradients are applied when necessary to move fluid from the blood to the dialysate compartment.
Membrane and fluxDialyzer membranes come with different pore sizes. Those with smaller pore size are called �low-flux� and those with larger pore sizes are called �high-flux.� Some larger molecules, such as beta-2-microglobulin, are not removed at all with low-flux dialyzers; lately, the trend has been to use high-flux dialyzers. However, such dialyzers require newer dialysis machines and high-quality dialysis solution to control the rate of fluid removal properly and to prevent backflow of dialysis solution impurities into the patient through the membrane. Dialyzer membranes used to be made primarily of cellulose (derived from cotton linter). The surface of such membranes was not very biocompatible, because exposed hydroxyl groups would activate complement in the blood passing by the membrane. Therefore, the basic, �unsubstituted� cellulose membrane was modified. One change was to cover these hydroxyl groups with acetate groups (cellulose acetate); another was to mix in some compounds that would inhibit complement activation at the membrane surface (modified cellulose). The original �unsubstituted cellulose� membranes are no longer in wide use, whereas cellulose acetate and modified cellulose dialyzers are still used. Cellulosic membranes can be made in either low-flux or high-flux configuration, depending on their pore size. Another group of membranes is made from synthetic materials, using polymers such as polyarylethersulfone, polyamide, polyvinylpyrrolidone, polycarbonate, and polyacrylonitrile. These synthetic membranes activate complement to a lesser degree than unsubstituted cellulose membranes. Synthetic membranes can be made in either low- or high-flux configuration, but most are high-flux. Nanotechnology is being used in some of the most recent high-flux membranes to create a uniform pore size. The goal of high-flux membranes is to pass relatively large molecules such as beta-2-microglobulin (MW 11,600 daltons), but not to pass albumin (MW ~66,400 daltons). Every membrane has pores in a range of sizes. As pore size increases, some high-flux dialyzers begin to let albumin pass out of the blood into the dialysate. This is thought to be undesirable, although one school of thought holds that removing some albumin may be beneficial in terms of removing protein-bound uremic toxins.
Membrane flux and outcomeWhether using a high-flux dialyzer improves patient outcomes is somewhat controversial, but several important studies have suggested that it has clinical benefits. The NIH-funded HEMO trial compared survival and hospitalizations in patients randomized to dialysis with either low-flux or high-flux membranes. Although the primary outcome (all-cause mortality) did not reach statistical significance in the group randomized to use high-flux membranes, several secondary outcomes were better in the high-flux group . A recent Cochrane analysis concluded that benefit of membrane choice on outcomes has not yet been demonstrated . A collaborative randomized trial from Europe, the MPO (Membrane Permeabilities Outcomes) study,� comparing mortality in patients just starting dialysis using either high-flux or low-flux membranes, found a nonsignificant trend to improved survival in those using high-flux membranes, and a survival benefit in patients with lower serum albumin levels or in diabetics.
Membrane flux and beta-2-microglobulin amyloidosisHigh-flux dialysis membranes and/or intermittent on-line hemodiafiltration (IHDF) may also be beneficial in reducing complications of beta-2-microglobulin accumulation. Because beta-2-microglobulin is a large molecule, with a molecular weight of about 11,600 daltons, it does not pass at all through low-flux dialysis membranes. Beta-2-M is removed with high-flux dialysis, but is removed even more efficiently with IHDF. After several years (usually at least 5-7), patients on hemodialysis begin to develop complications from beta-2-M accumulation, including carpal tunnel syndrome, bone cysts, and deposits of this amyloid in joints and other tissues. Beta-2-M amyloidosis can cause very serious complications, including a spondylarthropathy, and often is associated with shoulder joint problems. Observational studies from Europe and Japan have suggested that using high-flux membranes in dialysis mode, or IHDF, reduces beta-2-M complications in comparison to regular dialysis using a low-flux membrane.
Dialyzer size and efficiencyDialyzers come in many different sizes. A larger dialyzer with a larger membrane area (A) will usually remove more solutes than a smaller dialyzer, especially at high blood flow rates. This also depends on the membrane permeability coefficient�K0 for the solute in question. So dialyzer efficiency is usually expressed as the�K0A � the product of permeability coefficient and area. Most dialyzers have membrane surface areas of 0.8 to 2.2 square meters, and values of�K0A ranging from about 500 to 1500 mL/min.K0A, expressed in mL/min, can be thought of as the maximum clearance of a dialyzer at very high blood and dialysate flow rates.
Reuse of dialyzersThe dialyzer may either be discarded after each treatment or be reused. Reuse requires an extensive procedure of high-level disinfection. Reused dialyzers are not shared between patients. There was an initial controversy about whether reusing dialyzers worsened patient outcomes. The consensus today is that reuse of dialyzers, done carefully and properly, produces similar outcomes to single use of dialyzers
Peritoneal dialysisPeritoneal dialysis (PD) is a treatment for patients with severe chronic kidney failure. The process uses the patient`s peritoneum in the abdomen as a membrane across which fluids and dissolved substances (electrolytes, urea, glucose, albumin and other small molecules) are exchanged from the blood. Fluid is introduced through a permanent tube in the abdomen and flushed out either every night while the patient sleeps (automatic peritoneal dialysis) or via regular exchanges throughout the day (continuous ambulatory peritoneal dialysis). PD is used as an alternative to hemodialysis though it is far less common. It has comparable risks and expenses, with the primary advantage being the ability to undertake treatment without visiting a medical facility. The primary complication with PD is a risk of infection due to the presence of a permanent tube in the abdomen.
MethodThe abdomen is cleaned in preparation for surgery, and a catheter is surgically inserted with one end in the abdomen and the other protruding from the skin. Before each infusion the area must be cleaned, and flow into and out of the abdomen tested. A large volume of fluid is introduced to the abdomen over the next ten to fifteen minutes. The total volume is referred to as adwell while the fluid itself is referred to as dialysate. The dwell can be as much as 2.5 litres, and medication can also be added to the fluid immediately before infusion. The dwell remains in the abdomen and waste products diffuse across the peritoneum from the underlying blood vessels. After a variable period of time depending on the treatment (usually 4-6 hours), the fluid is removed and replaced with fresh fluid. This can occur automatically while the patient is sleeping (automated peritoneal dialysis, APD), or during the day by keeping two litres of fluid in the abdomen at all times, exchanging the fluids four to six times per day (continuous ambulatory peritoneal dialysis, CAPD). The fluid used typically contains sodium, chloride, lactate or bicarbonate and a high percentage of glucose to ensure hyperosmolarity. The amount of dialysis that occurs depends on the volume of the dwell, the regularity of the exchange and the concentration of the fluid. APD cycles between 3 and 10 dwells per night, while CAPD involves four dwells per day of 2-2.5 litres per dwell, with each remaining in the abdomen for 4-8 hours. The viscera accounts for roughly four-fifths of the total surface area of the membrane, but the parietal peritoneum is the more important of the two portions for PD. Two complementary models explain dialysis across the membrane � the three pore model (in which molecules are exchanged across membranes which filter molecules, either proteins, electrolytes or water, based on the size of the pore) and the distributed model (which emphasizes the role of capillaries and the solution`s ability to increase the number of active capillaries involved in PD). The high concentration of glucose drives the exchange of fluid from the blood with glucose from the peritoneum. The solute flows from the peritoneal cavity to the organs, and thence into the lymphatic system. Individuals differ in the amount of fluid absorbed through the lymphatic vessels, though it is not understood why. The ability to exchange fluids between the peritoneum and blood supply can be classified as high, low or intermediate. High transporters tend to diffuse substances well (easily exchanging small molecules between blood and the dialysis fluid, with somewhat improved results frequent, short-duration dwells such as with APD) while low transporters filter fluids better (transporting fluids across the membrane into the blood more quickly with somewhat better results with long-term, high-volume dwells such) though in practice either type of transporter can generally be managed through the appropriate use of either APD or CAPD. Though there are several different shapes and sizes of catheters that can be used, different insertion sites, number of cuffs in the catheter and immobilization, there is no evidence to show any advantages in terms of morbidity, mortality or number of infections, though the quality of information is not yet sufficient to allow for firm conclusions.
ComplicationsThe volume of dialysate removed and weight of the patient are normally monitored; if more than 500ml of fluid are retained or a litre of fluid is lost across three consecutive treatments, the patient`s physician is generally notified. Excessive loss of fluid can result in hypovolemic shock or hypotension while excessive fluid retention can result in hypertension and edema. Also monitored is the color of the fluid removed: normally it is pink-tinged for the initial four cycles and clear or pale yellow afterwards. The presence of pink or bloody effluent suggests bleeding inside the abdomen while feces indicates a perforated bowel and cloudy fluid suggests infection. The patient may also experience pain or discomfort if the dialysate is too acidic, too cold or introduced too quickly, while diffuse pain with cloudy discharge may indicate an infection. Severe pain in the rectum or perinium can be the result of an improperly placed catheter. The dwell can also increase pressure on the diaphragm causing impaired breathing, and constipation can interfere with the ability of fluid to flow through the catheter.
Risks and benefitsPD is less efficient at removing wastes from the body than hemodialysis, and the presence of the tube presents a risk of peritonitis due to the potential to introduce bacteria to the abdomen; peritonitis is best treated through the direct infusion of antibiotics into the peritoneum with no advantage for other frequently used treatments such as routine peritoneal lavage or use of urokinase. The tube site can also become infected; the use of prophylactic nasal mupirocin can reduce the number of tube site infections, but does not help with peritonitis. Infections can be as frequent as once every 15 months (0.8 episodes per patient year). Compared to hemodialysis, PD allows greater patient mobility, produces fewer swings in symptoms due to its continuous nature, and phosphate compounds are better removed, but large amounts of albumin are removed which requires constant monitoring of nutritional status. The costs and benefits of hemodialysis and PD are roughly the same � PD equipment is cheaper but the costs associated with peritonitis are higher. There is insufficient research to adequately compare the risks and benefits between CAPD and APD; a Cochrane Review of three small clinical trials found no difference in clinically important outcomes (i.e. morbidity or mortality) for patients with end stage renal disease, nor was there any advantage in preserving the functionality of the kidneys. The results suggested APD may have psychosocial advantages for younger patients and those who are employed or pursuing an education. Other complications include hypotension (due to excess fluid exchange and sodium removal), low back pain and hernia or leaking fluid due to high pressure within the abdomen. PD may also be used for patients with cardiac instability as it does not result in rapid and significant alterations to body fluids, and for patients with insulin-dependent diabetes mellitus due to the ability to control blood sugar levels through the catheter. Hypertriglyceridemia and obesity are also concerns due to the large volume of glucose in the fluid, which can add as many as 1200 calories to the diet per day. Of the three types of connection and fluid exchange systems (standard, twin-bag and y-set; the latter two involving two bags and only one connection to the catheter, the y-set uses a single y-shaped connection between the bags involving emptying, flushing out then filling the peritoneum through the same connection) the twin-bag and y-set systems were found superior to conventional systems at preventing peritonitis.
FrequencyIn a 2004 worldwide survey of patients in end stage renal disease, approximately 11% were receiving PD, compared to the much more common hemodialysis. In the United Kingdom, South Korea and Mexico PD was more common than the world average, with the latter conducting most of its dialysis (75%) through PD.