Dialysis

Dialysis, or hemodialysis,rift gold is a process of separating substances from the blood. Three quarters of a million people worldwide suffering irreversible kidney failure are maintained today using what is commonly called the ‘‘artificial kidney,’’ or hemodialyzer, the first machine to substitute for a failing organ. Around 1960 and by coincidence two separate methods of treating irreversible renal failure developed almost simultaneously as practical treatments: dialysis and renal transplantation (see Organ transplantation).

The idea that death in uremia following kidney failure results from retention of solutes normally excreted by the kidneys emerged during the nineteenth century. Diffusion in gases or liquids was worked out in parallel, principally by Thomas Graham, with mathematical development by J. H. vant’Hoff. These two ideas underlie the possibility of treating kidney failure by dialysis of potentially toxic solutes from the blood, and hence the tissues and body water.

The first attempt to carry out in vivo, extracorporeal dialysis of blood was made in 1913 by John Jacob Abel (1857–1938) in Baltimore, Maryland, at the Johns Hopkins Hospital, together with Canadian physician Lawrence Rowntree and English biochemist Benjamin Turner. Extracorporeal circuits had been developed in the 1880s for perfusion of whole organs in situ or ex vivo. Dialysis needed a semipermeable membrane that would retain protein and cells but allow solutes to diffuse from the blood. A number of substances had been tried in the laboratory, but the best seemed to be collodion, developed for photography in the 1850s as sheets of cellulose dinitrate. Blood was difficult to dialyze since it clotted on contact with foreign surfaces, but about the turn of the century hirudin, the anticoagulant in leech saliva, became available in crude form, and Abel and colleagues used collodion and hirudin. Their design consisted of a number of collodion tubes immersed in a cylindrical glass bath of dialysis fluid; blood drawn from an artery was pumped through rubber tubes into the apparatus and back into a vein. They dialyzed dogs and showed urea could be removed, but they were more interested in separating physiologically active substances from blood. At a demonstration of their dialyzer in London in 1913, a staff writer at the London Times first used the term ‘‘artificial kidney.’’ The team broke up after 1915 and Abel did no more work on dialysis.

The first specific attempts to treat uremia by dialysis were by Georg Haas (1886–1971) of Giessen, Germany, initially in ignorance of Abel’s work. He built a machine very like Abel’s in 1923 and treated the first human patients by dialyzing their blood ex vivo and reinfusing it intermittently. He also used hirudin as an anticoagulant, but this substance was still crude and often toxic. His patients had irreversible chronic kidney failure and all died. Haas abandoned the work until 1927 when the new anticoagulant heparin was discovered by Henry Howell, again at Johns Hopkins, together with medical student Jay Maclean and later, retired pediatrician Emmett Holt. But Haas’ patients still died, and in the face of opposition from the medical establishment, he gave up for good in 1928.

In 1923 Heinrich Necheles (1897–1979) of Hamburg was dialyzing dogs deliberately made uremic, but with a machine incorporating a new design: a flat sandwich with multiple layers of another dialysis membrane, the peritoneum from calves. However, despite his interest in uremia, he used this technique only to prepare physiological extracts from blood in dogs.

Despite the use of heparin, dialysis stalled because collodion was too complicated to produce, too fragile, and too difficult to use. A new membrane, cellulose acetate, was introduced in 1908, marketed as ‘‘cellophane’’ in France in 1910. By 1930 the material was formed into tubes in Chicago by the Visking Company to make ‘‘skinless’’ sausages and was rapidly shown to be useful in the laboratory for dialysis. William Thalhimer (1884–1961) a New York pathologist and hematologist realized in 1937 from his experience of anticoagulating and storing blood that heparin together with cellophane tubing made a practical dialyzer a possibility. He built such a machine and dialyzed dogs, but as he did no clinical work himself he encouraged others to try it in humans. In the early 1940s four individuals tried and succeeded, each without any contact with others. In 1944 Jonathon Rhoads (1907–2002) of Philadelphia built and used a dialyzer with cellophane tubing wound in spiral on a frame within a bath of dialysis fluid and used it on a single patient. The dialysis worked, but the patient died, and he did no more. Toronto surgeon Gordon Murray (1894–1976), an expert on heparin and a colleague of Thalhimer, worked on dogs from 1940 to 1946 to perfect a similar design. In 1946 his first patient was treated three times and survived her acute kidney failure. He did only a few dialyses over the next five years, also designing and using a flat-plate sandwich type of dialyzer. Nils Alwall (1906–1986) in Lund, Sweden, worked on rabbits for four years or more before achieving success in humans in 1946. His design was similar to Murray’s but was notable in that it had an outer casing permitting the pressure around the spiral to be controlled so that ultrafiltration of excess fluid could be limited. Alwall continued working in dialysis until retirement and trained many people to use his first machines, mainly in Europe but also in Australia, Israel, and even the U.S.

The best known of these researchers is Willem Kolff (1911–). In September 1945 he performed the first successful dialysis with recovery of the patient in Kampen, Netherlands. Beginning in 1943 he dialyzed 16 other patients, all of whom died. Many of them, however, had irreversible kidney failure, and some improved briefly. Although Kolff never did any animal work, for the first time he established the size parameters necessary for human use. As a result, his machine had a much larger surface area. He employed a spiral of tubing wound around a large horizontal drum, laying halfway in an open bath of dialysate, which rotated with a coupling from a Ford car engine to allow blood to flow into the cellophane tubing. Kolff believed passionately in dialysis, and during the late 1940s he built and gave away a number of machines, sent plans everywhere so people could build their own, and toured the world to advertise the new technique.

Initially facing worldwide skepticism, he went to Cleveland, Ohio in 1950. His machine was improved in Boston by physician John Merrill, surgeon Carl Walter, and engineer William Olson. Despite its many obvious disadvantages (e.g., large priming volume and uncontrolled ultrafiltration), it continued in use until the early 1960s. One major factor in acceptance of dialysis treatment during the 1950s was that, unlike the milder forms of acute renal failure where conservative management was possible, dialysis made a major difference to survival in injured soldiers with severe but temporary renal failure during the Korean War (1950– 1952). New dialyzers that were much easier to use were introduced. These included the twin-coil kidney designed and built by Kolff and Bruno Watshinger of Vienna in only a couple of months in Cleveland in 1956, and the flat-plate sandwich design invented first by the chemists Leonard Skeggs (1918–) (who later invented automated clinical chemistry) and Jack Leonards, and, independently, Arthur McNeil in Buffalo, New York.

By the end of the 1950s physicians everywhere, having inadvertently started dialysis in patients with chronic irreversible disease, found a slow, miserable ‘‘second death’’ inevitable as the blood vessels vital for access became unusable. A solution came from the polymer industry in the form of plastic polyvinylchloride (PVC) electrical insulation tubing, which was already used for connecting patients to dialysis. Although it was first discovered in 1937, PTFE or teflon, which was not wettable and did not stimulate thrombosis in blood, became available in the 1950s. Seattle, surgeon Warren Wintershide pointed this out to the renal physician there, Belding Scribner (1925–). He then got an engineering colleague Wayne Quinton to bend the tubes using heat and make a shunt joining an artery and vein externally so that it could be closed off from the machine between dialyses but allow blood to flow through it continuously: Suddenly, long term dialysis for irreversible disease was possible. One or two patients who started on dialysis only a few years later in 1966 remained alive at the turn of the twenty-first century. The shunts were improved by the use of another new material, silicone rubber. Then in 1965, from experience with venipuncture while working in a blood bank, James Cimino (1927–) and his colleagues in New York introduced access to veins enlarged by a surgically created arteriovenous fistula. By the end of the decade, these had become almost universal, and external shunts were already obsolete.

Initially, the reusable and then (from 1968) disposable flat-plate and coil dialyzers already in use for acute renal failure were also used for longterm dialysis. However in the early 1960s engineers at the Dow company in Michigan learned to make hollow fibers less than 100 micrometers in diameter from numerous different polymers for proposed uses in water purification, and in medicine as membrane oxygenators. Dick Stewart (1917–), a physician and chemist working with Dow, suggested their use for hemodialysis, and the first capillary hollow-fiber dialyzers were used in humans in 1967. By 1980 they were the predominant type of dialyzer in use, and from 1990 onward, used almost universally. Their great advantage, apart from efficiency, is their small size: a 30 by 15 centimeter hollow-fiber dialyzer has the same capacity as Kolff’s original rotating drum dialyzer, which was more than one meter long and half a meter in diameter.

Commercial cellulose acetate dialyzing membranes continued in use until the 1990s when replaced by more permeable and more biocompatible synthetic compounds such as polysulfone. In addition, these more permeable membranes (of which the polyacrylonitrile AN-69 of 1969 is the prototype) are increasingly used to exploit convective rather than diffusive removal of solutes, as pioneered by Lee Henderson (1931–) in the U.S. and Eduard Quellhorst in Germany in the 1970s. This technology has been particularly effective in treatment of reversible acute renal failure in very ill patients,rift gold using continuous hemofiltration throughout the day.

The other major change in dialysis machinery was the introduction of continuous blending of dialysate from concentrated salt solutions and reasonably pure (but not sterile) water, pioneered by Arthur Babb for Scribner in Seattle in the early 1960s, and now universal. In addition, various online safety measures, starting in the 1950s with a bubble trap to prevent air entering the circulation and the measurement of dialysate temperature and ionic strength, have continued to be introduced through the years.