Dialysis

• ANATOMY OR SYSTEM AFFECTED: Abdomen, blood, circulatory system, kidneys, urinary system

DEFINITION: The artificial replacement of renal (kidney) function, which involves the removal of toxins in the blood by selective diffusion through a semipermeable membrane

Indications and Procedures

The two major functions of the kidneys are to produce urine, thereby excreting toxic substances and maintaining an optimal concentration of solutes in the blood, and to produce and secrete hormones that regulate blood flow, blood production, calcium and bone metabolism, and vascular tone. These functions can be impaired or even completely halted by kidney failure that may be related to diseases such as hepatitis and diabetes. The kidney is the only human organ with a function—that is, the excretion of toxic substances from the blood—that can be artificially replaced on a reliable and chronic basis. Although dialysis cannot duplicate the intricate processes of normal renal function, it is possible to provide patients with a tolerable level of life.

If a solute is added to a container of water, it will be distributed at a uniform concentration throughout the water. This process is called diffusion and results from the random movement of the solute molecules in the solvent; it can be seen as a chemical mixing of the solution. The mixing will ensure an even distribution of solute molecules throughout the solution. The time required for complete mixing depends on factors such as the nature of the solute, its molecular size, the temperature of the solution, and the size of the container. The process of dialysis is based on the diffusion of solute molecules (urea and other substances) from the blood or fluids of a patient to a sterile solution called dialysate. The artificial kidney or dialysis system is designed to provide controllable osmosis, or the transfer of water across a semipermeable membrane separating streams of blood (contaminated as a result of renal failure) and dialysate (a sterile solution). For solutes such as urea, the outflowing blood concentration is high, while the concentration in the inflowing dialysate is usually zero. The result is a concentration gradient that guarantees diffusion of urea molecules from the blood to the dialysate solution. The same process will take place for other toxins present in the blood but absent from the dialysate solution.

There are two types of clinical dialysis—hemodialysis and peritoneal dialysis. In hemodialysis, a dialyzer is used, which consists of a blood compartment, a membrane, and a dialysate compartment. In a perfect dialyzer, diffusion equilibrium would result in the blood and dialysate streams during passage through the device, and virtually all the urea and toxins contained in the inflowing blood stream would be transferred to the dialysate stream. This level of efficiency is not achieved, however, and for maximum efficiency, dialysate flow rate should be from two to two and one-half times the actual blood flow rate.

Several fundamental material and design requirements must be met in the construction of efficient dialyzers suitable for clinical use. First, the surfaces in contact with blood and the flow geometry must not induce the formation of blood clots. The materials used must be nontoxic and free of leachable toxic substances. The ratio of membrane surface area to contained volume must be high to ensure maximum transference of substances, and the resistance to blood flow must be low and predictable.

There are three basic designs for a dialyzer: the coil, parallel plate, and hollow fiber configurations. The coil dialyzer was the earliest design. In it, the blood compartment consisted of one or two membrane tubes placed between support screens and then wound with the screens around a plastic core. This resulted in a coiled tubular membrane laminated between support screens, which was then enclosed in a rigid cylindrical case. This design had serious performance limitations, such as a high hydraulic resistance to blood flow and an increase in contained blood volume as blood flow through the device was increased.

The coil design has been largely replaced by more efficient devices. In the parallel plate dialyzer, sheets of membrane are mounted on a plastic support screen and then stacked in multiple layers, allowing for multiple parallel blood and dialysate flow channels. The original design had problems with membrane stretching and nonuniform channel performance. Modern membrane supports were developed. The hollow fiber dialyzer is the most effective design for providing low volume and high efficiency, together with modest resistance to flow. Developed in the 1970s, the membrane is composed of tiny cellulose or synthetic hollow fibers about the size of a human hair. Between 7,000 and 25,000 of those fibers are enclosed in a cylindrical jacket, with the blood inlet and outlet at the top and bottom of the cylinder, and the dialysate inlet and outlet being simply expanded sections of the jacket itself. This is the most commonly used geometry for hemodialysis. Extreme care must be taken to ensure that all the extra fluids that might have entered the blood during dialysis are removed. Ultrafiltration refers to the removal of water from the blood during dialysis and is a critical component of the dialysis process.

The delivery system of a dialyzer provides on-line proportioning of water with dialysate concentrate and monitors the dialysate for temperature, composition, and blood leaks. It also controls the ultrafiltration rate and regulates the dialysate flow. The system usually includes a blood pump, blood pressure and air monitors, and an anticoagulant pump.

The composition of the dialysate is designed to approximate the normal electrolyte concentrations found in plasma and extracellular fluid; it contains calcium, magnesium, sodium, potassium, chloride, a buffer (bicarbonate), and lactic acid, maintained at a pH of 7.4. The water used in this preparation is purified, heated to between 35 and 37 degrees Celsius, and deaerated to prevent air embolism. An anticoagulant must be added in the process to prevent the formation of blood clots. Heparin is the most commonly used anticoagulant, mainly because its effect is immediate, is easily measured, and can be almost immediately terminated by adding protamine. Because of its high molecular weight and substantial protein binding, it is not dialyzable and will not be lost from the blood in the process.

Several types of synthetic and modified cellulosic polymers are commonly used in the manufacture of membranes for hemodialysis. Cellulosic membranes are generated from the plant product cellulose, such as cellulose acetate. Synthetic polymers used in hemodialysis membranes include polyacrylonitrile, polysulfone, polyethersulfone, polyethylene-co-vinyl alcohol, and polyamide. The choice between these materials depends on biocompatibility, permeability, selectivity, mechanical and chemical durability, and sterilization compatibility.

The development of efficient, permeable synthetic membranes and ultrafiltration control delivery systems reduced treatment time in some cases, improved uremic toxin removal, and reduced patient complications. Dialysis is a potentially lethal procedure, and careful monitoring of equipment and solutions is necessary. For example, the dialysate must be monitored for hypertonic or hypotonic conditions that can result in hemolysis and death, and the flow from the dialyzer outlet back to the patient must have, among other things, an air bubble detector and filters to remove clots.

Peritoneal dialysis involves the transfer of solutes and water from the peritoneal capillary blood to the dialysate in the peritoneal cavity and the absorption of glucose and other solutes from the peritoneal fluid into the blood. The physiology of this process is less understood than that of hemodialysis. The process involves introducing a specific volume of dialysate into the peritoneal cavity and then removing it after the dialysis process is complete. The primary types of peritoneal dialysis include continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD).

Also called automated peritoneal dialysis (APD), CCPD is a nightly treatment performed by an automated machine called a cycler. Cyclers are semi-automated systems with simple operation and a low initial expense, providing basically trouble-free performance. However, they are expensive in the long run because they use premixed dialysates and many disposable components. Overnight, the machine completes three to five fluid exchanges in eight to twelve hours. While most patients use CCPD overnight, it can be used at any time of day.

CAPD is a versatile technique that does not require a machine because the inflow and outflow of dialysate are done manually by gravity. With approximately two liters of dialysate used per exchange, the procedure typically takes about thirty minutes and must be completed three to five times daily. This is a safe and effective method of dialysis.

For peritoneal dialysis, the dialysate includes dextrose, lactate, sodium, calcium, and magnesium salts. An anticoagulant such as unfractionated heparin can be added when needed, such as if blood is seen in the peritoneal fluid. Other substances—such as insulin for patients with and without diabetes, antibiotics in cases of peritonitis, and bicarbonate to prevent abdominal discomfort—can also be added without major complications.

Peritoneal dialysis may be a better choice than hemodialysis for certain patients when factors such as coronary artery disease, diabetes mellitus, age, or severe hemodialysis-related symptoms are present. It is also a convenient choice for patients who live far from a dialysis center.

Uses and Complications

Hemodialysis is used in patients with acute and chronic renal failure. Some individuals, however, do not tolerate hemodialysis well, such as children, infants, older patients, diabetics, and survivors of traumatic injuries. Therefore, the selection of patients for this procedure must be closely monitored. The process can also be used for the treatment of drug overdose (since drugs can be removed from the blood during the dialysis procedure) and hypercalcemia, an excess of calcium.

For many years, peritoneal dialysis was reserved for the treatment of acute kidney injury (AKI), formerly called acute renal failure (ARF), or for those patients awaiting transplantation or the availability of hemodialysis. Although it is used principally for the treatment of patients with end-stage renal disease, it remains a valuable tool in the management of AKI because of its simplicity and widespread availability. Essentially, it can be provided in any hospital by most internists or surgeons without the need for specially trained nephrology personnel. It also avoids the need for systemic anticoagulation, making it a good choice for patients in the immediate postoperative period with severe trauma, intracerebral hemorrhage, or hypocoagulable states. It is most suitable for patients with an unstable cardiovascular system, as well as for pediatric or older patients. It may be impossible to use, however, in postsurgical patients with many abdominal drains, with hernias, or with severe gastroesophageal reflux.

For many years, peritoneal dialysis was not used for patients with chronic kidney disease (CKD) because of the problems involved in the maintenance of permanent peritoneal access, the inconvenience of manual dialysate exchanges, the high rate of peritonitis observed in these patients, and the rapid progress made in hemodialysis in the early 1960s. The advent of a safe, permanent peritoneal catheter in the late 1960s and the simultaneous development of automated reverse osmosis peritoneal delivery systems created new interest in the technique and resulted in safer, more effective systems. Peritoneal dialysis can also be used or is recommended for: patients with diabetes, since it provides a continuous source of insulin and also has the advantage of providing blood pressure control; patients with edema, since the process is useful in the treatment of intractable edema states such as congestive heart failure; and for patients with pancreatitis who experience the release of pancreatic enzymes into the abdominal cavity and their subsequent absorption into the circulation. For the latter, the removal of the enzymes through peritoneal dialysis may prevent the necrotic process. Individuals exhibiting hypothermia as a consequence of accidental exposure, cold water immersion, central nervous system disorders, intoxication, or burns can be treated by performing peritoneal dialysis with dialysate solutions between 40 and 45 degrees Celsius. This will bring the body back to a stable temperature in a few hours, and, if the cause of the hypothermia is intoxication, the drugs causing the condition can be removed at the same time. Continuous renal replacement therapy (CRRT) can be used in a similar way as peritoneal dialysis for patients who are hemodynamically unstable in the intensive care unit.

Perspective and Prospects

As early as the seventeenth century, the relationship between blood and various diseases was known. At that time, however, great difficulties existed in the transport and study of blood. By the nineteenth century, the techniques for entering the blood vessels had been refined. The dangers of air embolization (air entering the patient) and clotting were well recognized. Prior to 1850, there was no treatment for patients with renal failure, but crude methods such as applying heat, immersing in warm baths, bloodletting, or administering diaphoretic (perspiration-inducing) mixtures of nitric acid in alcohol and wine were commonly used. (In fact, diaphoretic mixtures and bloodletting for renal failure were used as late as the 1950s.)

In 1854, Thomas Graham, a Scottish chemist, presented a paper on osmotic force, which was the first reference to the process of separating a substance using a semipermeable membrane. His definitions and experimental proofs of the laws of diffusion and osmosis form the foundation upon which dialysis is based. Between 1872 and 1900, the control of membrane manufacture and the dialysis of animal blood were critical developments. One of the key turning points in the development of dialysis occurred in 1913, when John Jacob Abel, using anticoagulants, created the first extracorporeal device that could be used to diffuse a substance from blood and developed methods to quantify this diffusion. World War I brought the development of the first plate dialyzer by Heinrich Necheles, a German-born physician. It included an air bubble trap, continuous blood flow, and an entry port for a saline solution to be used as dialysate; it was only used for animals. George Haas must be credited as the first to perform dialysis on a uremic human in October 1924. He used heparin, an anticoagulant discovered by William H. Howell and Luther E. Holt, two Americans. Haas had all the pieces together: a dialyzer with a large surface area, a workable membrane, a blood pump, and an anticoagulant.

The emergence of manufactured membranes in the 1930s (such as cellophane, which allows small molecules to pass through it) was crucial in the development of the technique. The lifesaving potential of an artificial kidney was shown by Willem Kolff, a physician from the Netherlands, who saved a patient from coma. His classic work New Ways of Treating Uraemia, published in 1947, laid out the principles that are still used and was the first manual for the treatment of patients undergoing hemodialysis. In the United States, the first clinical dialysis was performed on January 26, 1948, at Mt. Sinai Hospital in New York City, by physicians Irving Kroop and Alfred Fishman. Many groups were developing artificial kidney devices and programs between 1945 and 1950. The first complete artificial kidney system became commercially available in 1956, and the first home patient was treated in 1964 by Belding Scribner of the University of Washington.

Soon, the dialyzing fluid delivery systems became smaller and easier to use; the designs were simplified and made more compact, and a better understanding of the patient's physiology was obtained. Calcium depletion, bone disease, neuropathy, dietary management, and anemia were being closely examined to determine the optimal amount of dialysis required for effective treatment. The late 1960s brought the miniaturization of the systems, in-home care, and lower prices. In fact, in 1973, US legislation provided payment through the Social Security system for the care of patients on dialysis.

In the latter part of the 1970s, a shift to totally automated systems and an emphasis on negative-pressure dialysis had major impacts, resulting in a move from coil to hollow-fiber dialyzers. Some patients, however, such as patients with diabetes, children, and older patients, did not tolerate hemodialysis well. Therefore, a closer look was taken at peritoneal and automated peritoneal dialysis delivery systems. The earliest reference to peritoneal diffusion was in 1876, and in 1895, it was formally presented as an alternative to remove toxins from the bloodstream. Nevertheless, peritoneal dialysis lay dormant until the 1940s. The basic procedure of using solutions and instilling them into the peritoneal cavity to reduce the toxin levels in the blood was first used in 1945 by a group of physicians in Beth Israel Hospital in Boston. The full implications of its use came in the late 1970s, with the development of reverse osmosis technology and the introduction of continuous ambulatory peritoneal dialysis. In the 1980s, the introduction of continuous intermittent peritoneal dialysis gave patients yet another treatment option.

One of the main goals of the medical community and industry is to provide the quality of care that minimizes the burden of those afflicted with renal disease. The main goal, however, remains to obtain the necessary knowledge to understand the causes of progressive renal failure and prevent, control, or eliminate the consequences of renal disease. In the twenty-first century, despite years of scientific advancements, dialysis remained an expensive, time-consuming procedure. In the first decades of the twenty-first century, the number of people requiring dialysis increased globally, particularly in low-income and developing nations, which lacked the resources to care for these individuals.

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