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Willem Johan “Pim” Kolff

2009; Wiley; Volume: 38; Issue: 5 Linguagem: Inglês

10.1002/dat.20335

1932-6920

Eli A. Friedman,

Clinical Nutrition and Gastroenterology

When Willem Johan "Pim" Kolff died in Philadelphia on February 11, three days before his 98th birthday, the world lost the individual who shaped the bionic global transformation of medical care more than any other person. Born in Leiden, Netherlands on February 14, 1911, Kolff gained an interest in medicine from his father, Jacob Kolff, a physician, who directed the tuberculosis sanatorium in the town of Beekbergen. Following in his father's footsteps, Kolff opted for a medical career and graduated from the University of Leiden in 1938. He started postgraduate studies at the University of Groningen under the Department of Medicine's Jewish director, Professor Leo Polak Daniels. Consequent to Germany's invasion of the Netherlands in May 1940, both Polak and his wife committed suicide. Unwilling to work for his Nazi-appointed successor, Kolff resigned and relocated to Kampen City Hospital as its first internist, with an annual salary of $3,000. Medical practice under the German occupation stimulated Kolff's innate curiosity, motivating unanticipated engagement with some of the problems he faced, such as how to conceal the presence of some patients receiving care (such as Jews). Kolff established the first blood bank in Europe at Hague City Hospital in 1942, an accomplishment for which he was awarded the Karl Landsteiner Red Cross Medal. Disquieted by inefficacious interventions available to treat a 22-year-old man dying from renal failure, Kolff began his quest to create an alternative in the form of an artificial kidney. Remarkably, as concisely recounted in his 1946 text "New Ways of Treating Uremia," Kolff knew that the uremic syndrome was an intoxication induced by retained metabolites that, if extracted, might permit life prolongation. Among possible means to remove purported toxic retained solutes, Kolff listed: 1.) skin by induced sweating or hot bath immersion, and 2.) serous membranes, including the peritoneum by lavage, and the gastrointestinal tract by gavage. Based on the thinking of the time, Kolff dismissed both organ transplants for uremia because transplanted organs "atrophy in a short time" and the results of crossed blood transfusion that had been tested in dogs: "One does not know beforehand how the kidneys of the healthy donor would react," he said. Even in 1942, Kolff theorized that a maintenance uremia therapy had to be repetitive as in intestinal lavage: "It is far too soon to predict that those hopeless cases of chronic nephritis may perhaps be brought to lead useful lives. In the daytime they would work, and at night they would keep their ileal lavage going." Kolff's experiments narrowed their focus to extracorporeal extraction of solutes from blood kept liquid by anticoagulation, through the wall of inexpensive cellophane "sausage casing" produced for hot dogs by the American Visking Corporation in Chicago. Secret nighttime fabrication of a prototype artificial kidney was done at the Kampen Enamel Factory that had been restricted to manufacture of pots and pans for the German military. Comprised of an aluminum frame made of parts from a downed German plane, Kolff's first device had a rectangular tub with 70–100 liters of fluid circulated by a Ford Model T water pump in which a sewing machine motor rotated a drum upon which 30 to 40 meters of blood-filled cellophane tubing with a surface area of approximately 2.4 square meters was wrapped with blood moving from top to bottom by gravity (Figure 1). Under German occupation of the Netherlands, in the small town of Kampen, Kolff built a horizontal rotating drum artificial kidney with a sewing machine motor (A), attached to a bicycle chain that turned a drum (B), on which circulating blood within cellophane tubing was exposed to dialysate in a 100 liter porcelain tank (C) with the tubing mounted on a drum built of wooden slats (D). If you can give someone a happy life you should do it. If it cannot be a happy life you should not.—Willem Kolff Cautiously increasing the volume of blood samples dialyzed to 100 mL in sequential treatments lasting up to 17 hours, Kolff estimated that his rotating drum had a urea clearance of 140 mL/min, removing as much as 268 g of urea in a single dialysis. To remove excess water, dialysate osmolality was increased by adding glucose to the salt and bicarbonate mixture. Kolff's team treated 16 patients between March 1943 and July 1944—15 of whom died, with questionable benefit of dialysis on the sole survivor. Due to a lack of supplies, staff, and food, Kolff suspended dialysis for 14 months until the end of World War II when, on September 11, 1945, he performed an 11-and-a-half hour dialysis on 80 L of blood causing his 17th patient, a 68-year-old woman in a coma attributed to the hepatorenal syndrome, to awaken. She became the first long-term survivor of dialysis. Once Kolff documented the potency of his artificial kidney in reversible, otherwise fatal acute kidney failure, his pace intensified into a whirlwind of building artificial kidneys and establishing dialysis units in the Netherlands. He donated rotating drum devices to Mount Sinai Hospital in New York, McGill University in Montreal, Hammersmith Hospital in London, and what was to become Jagiellonian University in Krakow, Poland. Completing documentation of the methodology and benefits of dialysis treatments, Kolff gained a PhD summa cum laude in 1946 at the University of Groningen for his thesis. He visited Mount Sinai Hospital instructing medical residents in the use of his rotating drum so that the first dialysis in the United States was performed in January 1948 on a woman who survived mercury-induced acute kidney failure after an abortion. Invited to Harvard's Peter Bent Brigham Hospital in Boston, Kolff assisted Carl W. Walters, MD, and John P. Merrill in redesigning his device as the Kolff Brigham Artificial Kidney, directly connected to the patient by surgical cannula via a split coupling at the inlet and outlet of the rotating drum to prevent twisting of the cellulose membrane tubing (Figure 2). At a cost of $5,600 in 1948, this became the standard artificial kidney sold to 40 institutions all over the world from Tokyo to Chile. Merrill's basic studies of the Kolff Brigham Kidney, reported in the "Journal of Clinical Investigation," validated the scientific basis of dialytic therapy as applied to both identical twin kidney transplants and a new perspective on the management of kidney failure (Figure 3). Dr. Paul E. Teschan, during the Korean War, in 1952, utilized the Kolff Brigham artificial kidney on site to treat acute kidney failure extending thinking that later devised both home hemodialysis and prototypes of a wearable artificial kidney. Termed the Kolff Brigham Artificial Kidney, the 1948 modified rotating drum device priced at $5,600, as constructed of stainless steel with a Plexiglas hood. Newly designed couplings allowed direct attachment of surgical cannule to the patient's blood system without twisting of the cellulose membrane tubing. Dialyzer clearance was adjustable by varying the number of wraps of tubing. On the boardwalk at Atlantic City, NJ, Kolff (left) and John P. Merrill (right) converse between sessions of the newly formed American Society for Artificial Internal Organs in 1960. During a 1950 second lecture tour in the U.S. Kolff was recruited by Dr. Irvine Page to establish a Department of Artificial Organs at the Cleveland Clinic Foundation. With a goal of fabricating a cardiac substitution device Kolff's team, in 1957, implanted an artificial heart in a dog who survived for 90 minutes. Prototype intra-aortic balloon pumps were tested in 1961 as a bridge to ultimate artificial heart insertion. Toward this objective, Dr. Keith Reemtsma, in 1967, asked Kolff to relocate to the University of Utah in Salt Lake City to establish a program leading to an artificial heart. In collaboration with veterinary surgeon Dr. Donald Olson and his student, Dr. Robert Jarvik, the first totally artificial heart was tested in a calf and subsequently, in 1982, implanted by Dr. William DeVries in patient Barney Clark who survived for 112 days. With this front-page event, Kolff championed the first successful bionic substitution of a second vital organ. No surprise, therefore, that "Life Magazine," in September 2002, included Kolff in its listing of the 100 most important Americans of the 20th Century. Kolff's introduction of the artificial kidney fostered development of nephrology as a discipline, though his multiple contributions to medicine and current life go far beyond the boundary of kidney care. Table I lists 23 occupations that arose from the ability to extend life by dialysis including kidney transplantation. Merrill and Kolff created the climate for Belding H. Scribner's introduction of "chronic dialysis" converting irreversible uremia from an inevitably fatal disease to a chronic disorder in which more than one million patients who would have died are now under treatment (Figure 4). Dialysis sustained life and, in turn, motivated the extension of kidney transplantation from a novel therapy limited to young identical twins to the best option for uremia including children and geriatric patients in kidney failure. In his mid 60s, Kolff (left) stands with Belding H. Scribner (right) in the exhibition hall of the 1984 annual meeting of the American Society for Artificial Internal Organs. Both of these innovative inventors, scientists, and futurists, share credit for establishing hemodialysis as the most important and prevalent current therapy for irreversible uremia. In addition to the original thinking that envisioned organ replacement by machines, Kolff was an exceptional humanitarian. Throughout the horrific occupation of The Netherlands in World War II, Kolff afforded assistance to Jews and members of the resistance seeking to avoid death by German occupiers. As an example of his unique approach to all problems, Kolff fed Jews picric acid to turn their skin yellow knowing that German hospital administrators feared contracting hepatitis and avoided all contacts with jaundiced patients. That Kolff was always switched on is remarkably evident by his behavior as he, together with Scribner, was awarded America's highest honor for medical research, the Lasker Prize. When he accepted the award, he opened his vest to reveal that he was wearing his latest prototype of an artificial lung (Figure 5). Always seeking opportunities to surprise and engage his audience, Kolff, about to accept his Lasker Award statue in 2002, seen in the right foreground, opens his vest to show that he is wearing the latest model of his artificial lung. Kolff was awarded more than 150 prizes, plaques, and awards, causing the University of Utah to construct a designated building for their display, and the city of Kampen to erect a statue of him. He authored more than 600 articles and more than 10 books. He founded and was the first president of the American Society for Artificial Internal Organs, and co-founded the International Society for Artificial Organs.6 Kolff, vibrant at age 94. Recounting his concept of how artificial organs may impact life, Kolff advised the Dutch Organization of Kidney Patients in their magazine "Wisselwerking [Interaction]" that: "If you can give some one a happy life you should do it, if it cannot be a happy life you should not. When someone has an artificial heart and he has enough (of life) he should have a little key that he can turn it off. But, with a code, mind you, so his grandchildren cannot switch him off." Personally, Kolff's creativity not only motivated my choice of profession after meeting him as Merrill's fellow but, decades later, permitted my late wife to have 17 additional years of life after onset of kidney failure. I count Kolff as my hero, who together with other exceptional artificial organ pioneers, opened our "Age of Bionics for Any Season." D&T thanks Dr. Friedman for generously sharing his private collection of photographs for this article.