Process of removing blood from a patient with kidney failure, purifying it with a hemodialyzer (artificial kidney), and returning it to the bloodstream. Many substances (including urea and inorganic salts) in the blood pass through a porous membrane in the machine into a sterile solution; particles such as blood cells and proteins are too large to pass. This process controls the acid-base balance of the blood and its content of water and dissolved materials.
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In medicine, hemodialysis (also haemodialysis) is a method for removing waste products such as potassium 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.
The 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, and also, potassium and phosphate, diffuse into the dialysis solution. However, concentrations of sodium and chloride are similar to those of normal plasma to prevent loss. 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.
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’d 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. Firstly, 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 40 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 .
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.
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.
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.
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.
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.