08 January 2009

Artificial kidney

The invention A machine that removes waste end-products and poisons out of the blood when human kidneys are not working properly. The people behind the invention John Jacob Abel (1857-1938), a pharmacologist and biochemist known as the “father of American pharmacology” Willem Johan Kolff (1911- ), a Dutch American clinician who pioneered the artificial kidney and the artificial heart. Cleansing the Blood In the human body, the kidneys are the dual organs that remove waste matter from the bloodstream and send it out of the system as urine. If the kidneys fail to work properly, this cleansing process must be done artifically—such as by a machine. John Jacob Abel was the first professor of pharmacology at Johns Hopkins University School of Medicine. Around 1912, he began to study the by-products of metabolism that are carried in the blood. This work was difficult, he realized, because it was nearly impossible to detect even the tiny amounts of the many substances in blood. Moreover, no one had yet developed a method or machine for taking these substances out of the blood. In devising a blood filtering system, Abel understood that he needed a saline solution and a membrane that would let some substances pass through but not others. Working with Leonard Rowntree and Benjamin B. Turner, he spent nearly two years figuring out how to build a machine that would perform dialysis—that is, remove metabolic by-products from blood. Finally their efforts succeeded. The first experiments were performed on rabbits and dogs. In operating the machine, the blood leaving the patient was sent flowing through a celloidin tube that had been wound loosely around a drum. An anticlotting substance (hirudin, taken out of leeches) was added to blood as the blood flowed through the tube. The drum, which was immersed in a saline and dextrose solution, rotated slowly. As blood flowed through the immersed tubing, the pressure of osmosis removed urea and other substances, but not the plasma or cells, from the blood. The celloidin membranes allowed oxygen to pass from the saline and dextrose solution into the blood, so that purified, oxygenated blood then flowed back into the arteries. Abel studied the substances that his machine had removed from the blood, and he found that they included not only urea but also free amino acids. He quickly realized that his machine could be useful for taking care of people whose kidneys were not working properly. Reporting on his research, he wrote, “In the hope of providing a substitute in such emergencies, which might tide over a dangerous crisis . . . a method has been devised by which the blood of a living animal may be submitted to dialysis outside the body, and again returned to the natural circulation.” Abel’s machine removed large quantities of urea and other poisonous substances fairly quickly, so that the process, which he called “vividiffusion,” could serve as an artificial kidney during cases of kidney failure. For his physiological research, Abel found it necessary to remove, study, and then replace large amounts of blood from living animals, all without dissolving the red blood cells, which carry oxygen to the body’s various parts. He realized that this process, which he called “plasmaphaeresis,” would make possible blood banks, where blood could be stored for emergency use. In 1914, Abel published these two discoveries in a series of three articles in the Journal of Pharmacology and Applied Therapeutics, and he demonstrated his techniques in London, England, and Groningen,The Netherlands. Though he had suggested that his techniques could be used for medical purposes, he himself was interested mostly in continuing his biochemical research. So he turned to other projects in pharmacology, such as the crystallization of insulin,and never returned to studying vividiffusion. Refining the Technique Georg Haas, a German biochemist working in Giessen,West Germany, was also interested in dialysis; in 1915, he began to experiment with “blood washing.” After reading Abel’s 1914 writings,Haas tried substituting collodium for the celloidin that Abel had used as a filtering membrane and using commercially prepared heparin instead of the homemade hirudin Abel had used to prevent blood clotting. He then used this machine on a patient and found that it showed promise, but he knew that many technical problems had to be worked out before the procedure could be used on many patients. In 1937,Willem Johan Kolff was a young physician at Groningen.He felt sad to see patients die from kidney failure, and he wanted to find a way to cure others. Having heard his colleagues talk about the possibility of using dialysis on human patients, he decided to build a dialysis machine. Kolff knew that cellophane was an excellent membrane for dialyzing, and that heparin was a good anticoagulant, but he also realized that his machine would need to be able to treat larger volumes of blood than Abel’s and Haas’s had. During World War II (1939-1945), with the help of the director of a nearby enamel factory, Kolff built an artificial kidney that was first tried on a patient on March 17, 1943. Between March, 1943, and July 21, 1944, Kolff used his secretly constructed dialysis machines on fifteen patients, of whom only one survived. He published the results of his research in Acta Medica Scandinavica. Even though most of his patients had not survived,he had collected information and developed the technique until he was sure dialysis would eventually work. Kolff brought machines to Amsterdam and The Hague and encouraged other physicians to try them; meanwhile, he continued to study blood dialysis and to improve his machines. In 1947, he brought improved machines to London and the United States. By the time he reached Boston, however, he had given away all of his machines. He did, however, explain the technique to John P.Merrill, a physician at the Harvard Medical School, who soon became the leading American developer of kidney dialysis and kidney-transplant surgery. Kolff himself moved to the United States, where he became an expert not only in artificial kidneys but also in artificial hearts. He helped develop the Jarvik-7 artificial heart (named for its chief inventor,Robert Jarvik), which was implanted in a patient in 1982. Impact Abel’s work showed that the blood carried some substances that had not been previously known and led to the development of the first dialysis machine for humans. It also encouraged interest in the possibility of organ transplants. After World War II, surgeons had tried to transplant kidneys from one animal to another, but after a few days the recipient began to reject the kidney and die. In spite of these failures, researchers in Europe and America transplanted kidneys in several patients, and they used artificial kidneys to take care of the patients who were waiting for transplants. In 1954, Merrill—to whom Kolff had demonstrated an artificial kidney—successfully transplanted kidneys in identical twins.After immunosuppressant drugs (used to prevent the body from rejecting newly transplanted tissue) were discovered in 1962,transplantation surgery became much more practical. After kidney transplants became common, the artificial kidney became simply a way of keeping a person alive until a kidney donor could befound.

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