Search

In connection with the construction of one of the first practical dialysis machines, medical historians emphasize the work of the Swedish physician Nils Alwall. Together with his colleagues, he developed a device in the 1940s that could implement the combination of dialysis and ultrafiltration with membranes (cellophane tubes). Little known is the involvement of the physicians Lembit Norviit from Estonia and Adolfs Martins Steins from Latvia, both coauthors of the influential research article Clinical extracorporeal dialysis of blood with artificial kidney that was published in The Lancet in 1948 and the transfer of knowledge between Estonian, Latvian and Swedish researchers., (© 2023. The Author(s).)

Dr Willem J. Kolff was surely one of the greatest inventors/physicians/scientists/bioengineers of the last few hundred years. He was knighted (Commander of the Order of Oranje-Nassau) in 1970 by Queen Juliana of the Netherlands. In 1990, Life magazine published a list of its own 100 most important figures of the 20th century. Kolff stood in 99th place as the Father of Artificial Organs. Dr Kolff forged a path of innovative thinking and creativity that has had a huge impact on the quality of human life. His contributions to the development of the artificial kidney and dialysis, the heart-lung machine, the membrane oxygenator, potassium arrest of the heart, the AH, mechanical cardiac assistance, and other artificial organs, and his support and mentoring of hundreds to thousands of anesthesiologists, surgeons, and bioengineers throughout the world, have had a significant impact on anesthesiology and the medical community.

Willem Kolff (1911-2009), son of a physician, studied medicine in Leiden and specialised in internal medicine in Groningen. It was there that he started attempts to apply the phenomenon of dialysis in patients suffering from renal failure. He built the first prototypes of dialysis machines after his appointment as an internist in the municipal hospital in Kampen, during the Second World War. Indeed, in the first 15 patients he managed to decrease urea levels, resulting in temporary clinical improvement, but eventually they all died. It was not until after the war that dialysis helped a patient survive an episode of acute glomerulonephritis. After 1950 he continued his work on artificial organs in the United States (first in Cleveland and later, after 1967, in Salt Lake City). Although most of his work from then on revolved around the development of an artificial heart, he also contributed to the design of a compact, disposable apparatus for dialysis, the 'twin coil'. Haemodialysis also became feasible for patients with chronic renal failure after the 'Scribner shunt' (1960) provided easy access to the circulation. Peritoneal dialysis is another option. Excess mortality, mainly from cardiovascular disease, is still a largely unsolved problem.

Hemodialysis, which now provides life-saving therapy to millions of individuals, began as an exploratory attempt to sustain the lives of selected patients in the 1950s. That was a century after the formulation of the concept and determination of the laws governing dialysis. The first step in the translation of the laboratory principles of dialysis to living animals was the "vividiffusion" apparatus developed by John Jacob Abel (1859-1938), dubbed the "artificial kidney" in the August 11, 1913 issue of The Times of London reporting the demonstration of vividiffusion by Abel at University College. The detailed article in the January 18, 1914 of the New York Times, reproduced here, is based on the subsequent medical reports published by Abel et al. Tentative attempts of human dialysis in the decade that followed based on the vividiffusion apparatus of Abel and his materials (collodion, hirudin, and glass) met with failure and had to be abandoned. Practical dialysis became possible in the 1940s and thereafter after cellophane, heparin, and teflon became available. Abel worked in an age of great progress and experimental work in the basic sciences that laid the foundations of science-driven medicine. It was a "Heroic Age of Medicine," when medical discoveries and communicating them to the public were assuming increasing importance. This article provides the cultural, social, scientific, and medical background in which Abel worked, developed and reported his wonderful apparatus called the "artificial kidney."

March 9, 1960, was a milestone marker in end stage renal disease history - the date when a patient received the very first arteriovenous Scribner shunt. This began the era of maintenance or chronic hemodialysis. With long-term dialysis a reality, various new types of vascular access were developed. As the American Nephrology Nurses' Association celebrates its 40th anniversary, this article looks back to see just how far vascular access has come and what might be in store for the future.

Accumulation of knowledge requisite for development of hemodialysis started in antiquity and continued through Middle Ages until the 20th century. Firstly, it was determined that the kidneys produce urine containing toxic substances that accumulate in the body if the kidneys fail to function properly; secondly, it was necessary to discover the process of diffusion and dialysis; thirdly, it was necessary to develop a safe method to prevent clotting in the extracorporeal circulation; and fourthly, it was necessary to develop biocompatible dialyzing membranes. Most of the essential knowledge was acquired by the end of the 19th century. Hemodialysis as a practical means of replacing kidney function started and developed in the 20th century. The original hemodialyzers, using celloidin as a dialyzing membrane and hirudin as an anticoagulant, were used in animal experiments at the beginning of the 20th century, and then there were a few attempts in humans in the 1920s. Rapid progress started with the application of cellophane membranes and heparin as an anticoagulant in the late 1930s and 1940s. The explosion of new dialyzer designs continued in the 1950s and 1960s and ended with the development of capillary dialyzers. Cellophane was replaced by other dialyzing membranes in the 1960s, 1970s, and 1980s. Dialysis solution was originally prepared in the tank from water, electrolytes, and glucose. This solution was recirculated through the dialyzer and back to the tank. In the 1960s, a method of single-pass dialysis solution preparation and delivery system was designed. A large quantity of dialysis solution was used for a single dialysis. Sorbent systems, using a small volume of regenerated dialysis solution, were developed in the mid 1960s, and continue to be used for home hemodialysis and acute renal failure. At the end of the 20th century, a new closed system, which prepared and delivered ultrapure dialysis solution preparation, was developed. This system also had automatic reuse of lines and dialyzers and prepared the machine for the next dialysis. This was specifically designed for quotidian home hemodialysis. Another system for frequent home hemodialysis or acute renal failure was developed at the turn of the 21st century. This system used premanufactured dialysis solution, delivered to the home or dialysis unit, as is done for peritoneal dialysis.

Nowadays renal dialysis, with its sleek, compact machinery, is a routine, somewhat taken for granted procedure in our hospitals. The development of this life-saving apparatus, initiated by a young Dutch physician during the Nazi occupation of his country, is a fascinating story.

Time is a unique dimension of the universe, along with perhaps 10 dimensions of space, according to superstring theory. Our brain and its associated consciousness perceive time as a continuous unidirectional stream. Even though we appear to be able to move freely in three dimensions of space; time's arrow for us points only one way, the present eroding into the future to leave the past behind. For two millennia, time has been likened to a stream or river. In the West, for the past two centuries, time and change have been equated almost automatically with the idea of progress. However, change always brings with it loss as well as gain, and progress is far from inevitable. This remains true in the history of medicine. The history of any subject is full of blind alleys, which, although important at the time, generally become edited out in retrospect.

According to Herodotus, the use of charcoal was introduced in ancient Egypt; however only in 1773 Carl Willhelm Scheele utilized it for adsorbing gases. Finally, Hippocrates Yatzidis in 1963 demonstrated its binding capacity for toxic substances of endogenous or exogenous origin and used it for hemoperfusion systems.

Only very few remember Georg Haas as the scientist who--in 1924--was the first to successfully conduct an extracorporal hemodialysis on a patient in Giessen. Haas began his experiments in 1914 shortly after joining the Medical Clinic of the University of Giessen. Neither protocols nor any of the set-ups were preserved from these early experiments. In addition, the WW1 interrupted Haas' early experiments between 1917-1919. Until 1923 Haas himself never mentioned his early experiments. "Outside circumstances" and a "shortage of materials" (hirudin) prevented Haas from continuing his work on hemodialysis. Also, the early trials had disappointing results as the experimental animals, mostly dogs, died after a few hours. The hirudin preparations Haas had used turned out to be toxic. While the toxicity of the hirudin preparations prevented the application of dialysis in humans early on, the war with its many cases of nephritis provided new inspiration to develop dialyzing techniques. Haas experimented with reed tubes, calf peritoneum and paper membranes. None of these worked satisfactorily. Not until Pregl introduced collodion tubes was the first barrier overcome. Haas started experimenting with collodion tubes produced by himself. However, the toxicity problem with the hirudin preparations remained. Haas resumed the hemodialysis experiments in 1923. Significantly, 1923 was the year when Necheles published his work describing an alleged purified leech extract. Necheles' paper also described American experiments that focused on dialysis in animal trials. It was J. Abel of Baltimore who informed Haas that purified hirudin was available. After learning of this availability through the American studies in 1924, Haas conducted his first hemodialysis on a uremic patient in late 1924. This experiment lasted only 15 minutes and was without complications. A second dialysis attempt followed in 1925 and even lasted 30 minutes. Finally, four further experiments followed in 1926. The turning point was the availability of purified heparin from 1925 on. Haas, who in 1924 conducted the first dialysis using hirudin, in 1927 conducted the first hemodialysis using heparin. Further hemodialysis treatments followed. Haas concluded: "The problem of hemodialysis is still in the first steps of practical application. Nevertheless it could be shown that hemodialysis has developed sufficiently to find applicability even in patients with serious kidney ailments and irritable heart...Hemodialysis was not only well tolerated but also brought a temporary subjective improvement. Of course, the technical aspects of hemodialysis still need improvement and further development to qualify as detoxicant therapy." A look at the early history of the artificial kidney and its applicability to humans reveals that J. Abel conducted the first hemodialysis on experimental animals. It also becomes evident that Haas conducted the first hemodialysis in humans. The American experiments pursued the quantitative optimization of the method in animal trials, while Haas' experiments focused on the development of a therapeutic method following the principle "primum nil nocere."

Medicine in the technological era acquired many of the characteristics that concurrently marked other fields. So, by adopting procedures based on information obtained with instruments and devices, medicine developed an approach to illness that transformed it into a special form of technology. The collective effect of instrumentation deserves consideration and offers the historian opportunities for interpreting the interaction between physician and his patients in other than scientific and technological terms. The very construction of instruments and devices depends on the Author's ideas assembled with the basic theories of the time. For instance, at the end of the nineteenth century, when medical instruments became essential, the bacterial origin of diseases revolutionised their construction and application. In this context, the invention and use of the microscope became an outstanding feature of the clinical approach by disclosing the cellular universe. The microscope had become crucial in locating some major causes of physical suffering and death in man, and was considered the pre-eminent diagnostic instrument in medicine. In the nephrological field, the microscope drew the physician into a universe of physical changes that were concealed to the naked eye. The microscope made possible the verification of some of Bright's brilliant ideas, something that helped physicians classify glomerulonephritis. Many nephrologists confessed "how few things are established in this subject (nephrology) and how many more difficulties are established, we have learned by experience with the microscope". The modesty of this claim is striking. In nephrology, as in other fields, the admission of ignorance proved to be the beginning of wisdom. This wisdom, based on the admission of ignorance and assembled through the commitment and ingenuity of the pioneers of the dialysis treatment, led to the treatment of end-stage renal disease and the guarantee of success. The technique of haemodialysis has been enriched by the new lexicon, which expresses different ways and ideas on the removal of the solute.

Aminta Fieschi, a physician who is today remembered mainly for his contributions in the field of haematology, in the late 1940s devoted himself to the study of the treatment of uraemia. For this reason he commissioned, a manufacturer based in Milano, an artificial kidney, which was built on the design of the "rotating-drum kidney" described by Willem Kolff in 1947 in his epoch-making monograph "New Ways of Treating Uraemia". However, after using that artificial kidney in few patients Fieschi abandoned it due to dangerous cardiovascular complications, and shifted to the use of other safer techniques such as intestinal perfusion. This paper describes the main contributions of Fieschi in the field of nephrology as well as the features of artificial kidney he used, whose manufacturer has been identified and retraced after more than fifty years by the author.

In Italy the first attempts at haemodialysis, first in vitro and animals and then in humans, were carried out in the early 1950s by the surgeons Mario Battezzati e Carlo Taddei of Genoa with an artificial kidney of their own design. During the same years several other surgeons and urologists in Padua, Milan, Turin, Florence, Modena, Rome, Naples and Palermo designed their own artificial kidneys, which were used to treat anuric patients suffering from acute renal failure. The lively interest in artificial kidneys led, in 1954, to the organisation of a symposium on the subject. This was the first symposium of its kind not only in Italy but also at European level and was characterised by a wide discussion on all aspects associated with extracorporeal dialysis. In subsequent years the use of artificial kidneys continued to develop in several of the above-mentioned Italian centres, something that in the early 1960s led to the introduction of chronic haemodialysis. This paper shows how in Italy the use of artificial kidneys was characterised by intense experimental and clinical activity as well as original approaches to the many problems associated with the use of this technique.

Gordon Murray (1894-1976), a brilliant and innovative surgeon who spent the majority of his professional career at the University of Toronto, Ont., Canada, is properly credited with having performed the first successful hemodialyses in humans in North America. Neither he nor Kolff, working in the Netherlands, were aware of each other's work during the middle 1940s when wartime hampered communication. Murray's extensive investigations and experience in the use of heparin in vascular surgery laid the groundwork for the use of this anticoagulant with the artificial kidney. He first designed a coil dialyzer in which cellophane tubing was wound about a steel frame. His second-generation apparatus was a plate dialyzer. In all, he performed dialysis on 11 patients with presumed acute renal failure, 50% of whom survived. Those who died succumbed to sepsis or irreversible chronic renal failure. Not much has changed in 50 years., (Copyright 2002 S. Karger AG, Basel)

In 1994, Willem Kolff published his results on haemodialysis on humans. His achievements were based on 19th century medicine. Richard Bright had contributed to the knowledge of kidney diseases and Graham and Fick had described diffusion through semipermeable membranes. Some initial tests of haemodialysis had been performed by Abel and Haas in the beginning of the 20th century. But it was Kolff's publication that initiated three innovative decades of development of artificial kidneys: the development from sausage casing to the hollow fiber kidneys.

The development of hemodialysis from an experimental concept to a routine medical therapy is closely related to research, manufacturing and availability of dialysis membranes. Collodion, a cellulose-trinitrate derivative, was the first polymer to be used as an artificial membrane and played a central role in further investigations and applications. Basic studies on the mechanism of solute transport through membranes, like diffusion, were done by A. Fick and T. Graham using collodion as a membrane material. In vivo dialysis in animals and humans was performed with collodion by J. Abel in the USA and G. Haas in Germany. Cellophane and Cuprophan membranes replaced collodion later, because of their better performance and mechanical stability. However, due to its alleged lack of hemocompatibility, membranes made from unmodified cellulose lost their market share. They have been replaced by modified cellulosic and synthetic dialysis membranes which show a better hemocompatibility than unmodified cellulose membranes. Most of the new membrane materials are also available in high-flux modifications and for this reason suitable as well for more effective therapy modes, such as hemodiafiltration and hemofiltration. The success of hemodialysis as a routine therapy is also the success of membrane development, because both, a reproducible membrane production and an unlimited availability of dialysis membranes have increased the number of dialyzed patients to about 1 million patients worldwide in 1999.

Long-term hemodialysis for chronic renal failure first became possible with development of the Teflon shunt by Belding Scribner and coworkers at the University of Washington, Seattle, in 1960. Over the next 4 years, many of the advances in dialysis occurred in Seattle. These included recognition and treatment of complications such as malignant hypertension, gouty episodes due to uric acid accumulation, subcutaneous calcification, anemia, iron overload, and peripheral neuropathy. Technical advances included improving the shunt, and in collaboration with Professor A.L. Babb, development of a proportioning system to make dialysate from concentrate and water and the first automated home hemodialysis machine. Dr. Boen and Dr. Tenckhoff developed automated peritoneal dialysis equipment and peritoneal access devices. The world's first outpatient dialysis center, the Seattle Artificial Kidney Center, was established in 1962, and used an anonymous lay committee to select from medically suitable patients those to be treated by the center. This triage was an important step in the development of biomedical ethics, and in 1964, Scribner's presidential address to the American Society for Artificial Internal Organs discussed the problems of patient selection, termination of treatment, patient suicide, death with dignity, and selection for transplantation.

Since 1957, I have been well aware of Dr. Kolff's contribution in the field of artificial organs. Therefore, when I came to the United States, the first thing I knew I wanted to do was to meet Dr. Kolff. I finally met him on April 16, 1962 in Cleveland. At that time, I never dreamed that one day I would be working for him even though I had already been involved in the field of artificial organs. During the 3 years that I worked for Dr. Kolff, between April 1, 1964 and March 31, 1967, I obtained the basic training and foundation for succeeding him in the Department of Artificial Organs, Cleveland Clinic Foundation. During those first 10 years after succeeding Dr. Kolff, I devoted myself to reestablishing the department. He was always supportive of me in establishing my objective. Beginning in 1977, together with Dr. Kolff, I devoted my life to establishing and maintaining the International Society for Artificial Organs (ISAO) as the leading organization in the world for artificial organ technologies. Dr. Kolff was also supportive of this effort. Without his support, I, as well as others in the world who are involved in artificial organ technologies, believe that the ISAO would not be what it is today. We are very grateful to him for his contributions in this field.

Dr. Willem J. Kolff's imaginative venturesomeness in adopting "new ways of thinking" has served as an encouraging model for this author's research career. In appreciation of his leadership and beginning with the favorable results that attended the initial use of the Brigham-Kolff artificial kidney at a renal center in the Korean war, this presentation summarizes four experiences to illustrate how "new ways of thinking" produced new results and new research, namely, the concept and use of prophylactic daily hemodialysis; the use of a model of acute renal failure in rats to examine mechanisms of pathogenesis and means of prevention; the recognition of patients' uremic illness as an encephalopathy that can be quantified by appropriate measures; and the use of daily peritoneal dialysis and quantified EEGs in rats to explore relationships between dialysis-induced concentrations of potentially toxic solutes, quantified indices of symptomatic uremic encephalopathy, and concurrent, localized metabolic abnormalities in the brain. The results of these "new ways of thinking" suggest that we may ultimately come to understand the clinical uremic illness and its response to dialysis.