Originally published in Volume 43 Issue 2 of Artificial Organs, 28 January 2019
The feasibility of kidney transplantation had its foundation in advances in the dialysis management of patients with end-stage renal disease (ESRD). Dr. Willem Kolff invented the first clinically successful artificial kidney (AK) in medical history in 1944 in Kampen, The Netherlands with technical help from an engineer H.Th.J. Berk who was the director of an enamel company.1 It was a rotating drum AK. Development of the fundamental concept of hemodialysis by Dr. Kolff was the key to the future management of ESRD. In 1960, Dr. Belding Scribner and an engineer Wayne Quinton invented an external arteriovenous (A-V) shunt2 above the patientʼs wrist which permitted repeated dialysis.
In the 1960s, only 1 dialysis machine was available at major hospitals in the US including the University of Washington in Seattle, WA and the Cleveland Clinic Foundation (CCF) in Cleveland, OH and it was estimated that approximately 70 thousand people died of ESRD yearly. Dr. Scribnerʼs group could accept only 5 patients. Thus, he established a committee to select 5 “ideal” patients. Dr. Kolff had a different philosophy and believed in equality of humans. For him, it was “First come, first served.” However, Dr. Scribnerʼs patients lived relatively normal lives sometimes for many years, whereas Dr. Kolffʼs patients had distinctly inferior survival rates. Nevertheless, these dialysis advances established a platform from which further progress could be made, not only in the realm of hemodialysis but also on a new era of kidney transplantation.
I had been a fellow under Dr. Kolff since 1956 and he kindly promoted me to the staff in 1961. I attended the annual meeting of the American Society for Artificial Internal Organs in Atlantic City in April 1961. There I learned both Dr. John Merrillʼs group at Peter Bent Brigham Hospital in Boston3 and Dr. Jean Hamburgerʼs group at Hospital Necker in Paris4 had performed successful human kidney transplantations in a small number of patients at the beginning of 1954, starting with identical twins, related-live and cadaver donor kidney transplantations. I realized that successful kidney transplantation offered the prospect of a much superior long-term way of life than did chronic hemodialysis. I held on to that idea. Following morning rounds one day in mid-1961, after seeing the mounting problems for a restricted number of dialysis patients, I went to Dr. Kolffʼs office and told him about the activity in the new kidney transplant programs in Boston and Paris. I urged Dr. Kolff to organize a kidney transplant program at CCF. I thought that Dr. Kolff as the gifted inventor of dialysis who relentlessly dedicated himself to improve the equipment for and technical aspect of dialysis, would reject the transplant idea. To my surprise, Dr. Kolff said, “Sat (my nickname), you are right. It is an excellent idea. You are in charge of the transplant program. I will support you 100% and raise the seed money to start. You just concentrate on this PROJECT.”
Dr. Kolff then called and told his long-time friend, Dr. John Merrill that Sat wants to start the kidney transplant program at CCF and would like to learn about the program. Two weeks later, I went to Boston for 10 days and learned the essential clinical and laboratory aspects of the kidney transplant program. The first day there I was very impressed to see that a middle-aged male patient who had recently received a cadaver kidney transplant was walking around in the corridor with his wife. Before I visited to Boston, I went to the Pathology Department and checked the number of autopsies that were performed in the past 6 months. The average numbers were 15 cases, of which about 5 cases were possible donors. Thus, if we are well-organized, 10 cadaveric transplants could be done per month.
After I returned from Boston, Dr. Kolff and I thought clinical kidney transplantation is reasonable and established a Transplant Committee. The first meeting was held on November 27, 1962. Its members and their areas of responsibilities were: (1) Dr. Kolff and I take care of pre- and post-transplant clinical care of the patients including dialysis management; (2) Drs. Poutasse and Straffon perform the transplants; and (3) Dr. Donald Senhauser handled the pathology. The agendas were: (1) As human kidney transplant had already been shown to be feasible and successful, we would avoid wasting time with animal studies; (2) Set the criteria for accepting ESRD patients into the transplant program; (3) Selection of related-live and also cadaver donors; (4) Gain experience with cadaver kidney transplant first before doing related-live donor transplant; (5) Concentrate all efforts on deceased donor transplants; and (6) Medicines such as glucocorticoids and azathioprine (Imuran) would be used for anti-rejection.
At CCF according to the earliest medical record, the first kidney transplant was done on October 25, 1957. It was a cadaveric transplant from a 49-year-old man to a 23-year-old man. The allograft was transplanted at the left iliac fossa. He developed acute rejection and died 10 days later. The second cadaveric transplant was done from a 55-year-old woman to a 48-year-old woman on January 9, 1963 who lived only for 15 days. A 33-year-old man, transplanted on August 24, 1963, was the first cadaver kidney transplant patient who survived over 1 year post operatively. He was the third cadaver kidney transplant patient at CCF and actually lived over 2 years. The first live-related kidney transplant was done on April 1, 1963 from a 40-year-old mother to her 14-year-old daughter who lived for many years. In 1963, a total of 19 kidney transplants were done. Ten transplants were from live-related and 9 from cadaveric donors.
At all leading transplant centers in the nation, well-known general surgeons performed the transplants. However, Dr. Kolff chose urologists Drs. Poutasse and Straffon instead as Dr. Poutasse had successfully treated renal hypertension secondary to renal artery arteriosclerosis with renal artery endarterectomy.5
The National Institutes of Health (NIH) entered the clinical transplantation picture in 1963 and seventh report of the human kidney transplant registry was published in 1969.6 Its original physician members were; Drs. Thomas Starzl in Denver, CO, Joseph Murray and Benjamin Barnes in Boston, MA, David Hume in Richmond, VA, Keith Reemtsma in Salt Lake City, UT, John Najarian in Minneapolis, MN, Donald Martin in Los Angeles, CA, and myself in Cleveland, OH, USA. All were prominent surgeons except for me—an unknown physician except through Dr. Kolff. The NIH first asked Dr. Kolff to be a member, however, he said “Sat organized our transplant program. He should be a member.” Also, NIH chose Dr. Norman Shumway at Stanford University to perform the heart transplants and Dr. Thomas Starzl at the University of Colorado to perform the liver transplants. When the 2 groups standardized pre- and postoperative care, then other major medical centers will follow.
At one of NIH meetings, David Hume presented his experience on cadaver kidney transplant using car accident victims as donors. Then, Thomas Starzl showed his experience with a volunteered prisoner’s kidney. At a Q & A session, Hume stood up and said the car accident victims are better than the prisoners. Then Starzl replied that David has not developed TOLERANCE yet. Everyone laughed.
At CCF in 1960s when the cadaver kidney did not gain a satisfactory function at 4 weeks postoperatively, the allograft biopsy was routinely done to evaluate its pathophysiology. However, the biopsy was never done on live donor recipients to avoid complications. One day, I did a biopsy on a cadaveric recipient who developed massive bleeding and the allograft was removed. I felt very guilty and thought there must be some other way to evaluate the allograft viability. I consulted Dr. Ralph Alfidi at the radiology department who suggested to do a selective angiography.7 I also consulted Dr. Antonio Antunez at the Department of Radiation Therapy who recommended a scintigram.8 Both procedures helped to evaluate the allograft function.
The second Transplant Committee meeting was held on August 10, 1963 and its topics were; selection and preparation of deceased donors; care of recipients in the ICU postoperatively for 1 week and transfer to a single bed room on a regular floor; use of maximal sterile techniques for everyone who takes care of the recipient including staff, residents, nurses and housekeepers, and required weekly nose cultures.
In 1964, 5 living-related and 22 cadaveric transplants and in 1965 11 living-related and 48 cadaver transplants were done, respectively. Overall survival rates of cadaveric kidney transplants from January 1963 to December 1966 at CCF were 48% which was as good as the national average rate of living donor kidney recipients.9 A 29-year-old man who had a cadaveric kidney transplant on January 14, 1964 lived for 18 years without rejection and died of lymphoma. He was the longest survivor in the world at that time.
The effort to increase potential deceased organ donation was also enhanced by Dr. Kollfʼs idea in 1965 to create a Uniform Donor Card that people could carry in their wallet or purse. On the card were written the name of the donor and organs that could be retrieved upon the donor’s death. Because the viability of the kidneys could decline rapidly, the card emphasized that “Speed is Essential.” The instructions also stated “Whoever finds this card on a deceased person, call CCF immediately.”10
The third transplant committee meeting was held on October 20, 1965, focused on developing a cooperative program to obtain cadaver kidneys from regional hospitals. Drs. Straffon and I attended one of the monthly staff meeting at other hospitals to encourage their cooperation. Time was essential to transport cadaver kidneys from regional hospitals to CCF, so we asked for a police escort. The idea was good but it had a logistical problem. The representatives from major TV stations and local newspapers were at the police department awaiting any big news. When we called the police department to escort us, the police told the news media that they were escorting a car driven by a doctor from CCF to transport a cadaver kidney from another hospital. The news media immediately called their main offices and stations reported this event. The administration office at the CCF initially thought we called the news media. When a successful business man, Tom Meyer served the president of CCF from 1969 to 1972, he had offered his helicopter to transport cadaveric kidneys from hospital near surrounding cities.
As the numbers of deceased kidneys from other hospitals increased, it was necessary to construct a small container to transport the kidneys in a sterile condition. I had an idea and consulted the Clinicʼs machine shop. They made it from a small paint spray can to keep the kidney inside, which connected to a portable oxygen tank. The spray can was kept in a bucket filled with ice. This apparatus satisfied the need.
In 1965, I received unexpected calls from Drs. John Merrill and David Hume both of whom were trained at Peter Bent Brigham Hospital. They said because the survival rate of deceased donor kidney transplants was so poor that they were going to stop it. The cause of death was overwhelming infection secondary to severe leukopenia. I told them the cadaveric transplant program at CCF was satisfactory, so that we were encouraged to continue the program. When I analyzed these contrasting results, I realized their groups dialyzed recipients only when blood urea nitrogen increased over 150 mg/dL. The Boston group believed a mild uremia acts as immunosuppressant. In contrast, our group dialyzed the recipient twice weekly until the allograft regained function up to 4 weeks as if the recipient had no transplant. Then I wondered why? I suspected Imuran is not bound 100% to serum protein. Thus, a significant amount of it was dialyzed out, so severe leukopenia was prevented. Later, Dr. William Braun at CCF found that its metabolite, mercaptopurine is bound 30% to proteins and is partially dialyzable. Because of our excellent survival rate of 48% from cadaver kidney transplantation,9 the Cleveland Plain Dealer published a special Sunday supplement describing in detail our transplant program on March 1, 1964. LIFE Magazine also published our story as “Gift of Life from the Dead” in its edition on October 5, 1965.
Dr. Kolff left for the University of Utah in 1967 by invitation from his long-time friend, Dr. Keith Reemtsma, chief of surgery. Dr. Kolffʼs laboratory space at CCF was very small and was only half of the 6th floor of the Research Building. He promised Dr. Kolff a new 8 floor research building where he could work on a wide range of “artificial internal organs,” such as heart, eye, limb, and a portable wearable AK. I wanted to move with him but Dr. Kolff said CCF had been nice to me and supported my research projects. I do not want to destroy both dialysis and transplant programs which you and I developed. He told me to stay here and now on we will be friendly competitors.
Dr. Christian Barnard in Cape Town, South Africa did the first cadaveric cardiac transplant in the world on December 3, 1967. The patient died on the 18th post-operative day of pneumonia. At CCF on September 14, 1968, 3 transplants were done from a 25-year-old woman who had a car accident nearby and was taken to the emergency room at CCF. She soon died and her family agreed to donate her organs including the heart and kidneys. Dr. Rene Favaloro performed a cardiac transplantation on a 50-year-old man who had lived a normal life without rejection over 1 year. Since I had experience with anti-rejection drugs, I managed him postoperatively. One morning walking to the mailbox in his driveway, he suddenly collapsed and died of acute heart attack. Also from the same donor, 2 chronic dialysis patients received kidneys—one was a 21-year-old man and another a 29-year-old man. Both recipients lived normal lives without rejection for many years.
Urologists (not general surgeons) Drs. Poutasse and Straffon built and sustained the kidney transplant program at CCF. Dr. Poutasse left later in 1963, so in an early part of 1964 Dr. Straffon was the only transplant surgeon. He performed 4 transplants within 24 hours from 8 am on September 2 to 8 am on September 3, 1964 including 1 pre-scheduled with a live donor and 3 cadaver donor transplants. Nobody else in the world did 4 transplants within 24 hours until then. Later that year, Dr. Straffon recruited Dr. Bruce Stewart from the University of Michigan, Dr. William Kiser from NIH and Dr. Clarence Hewitt from Water Reed Army Hospital. Dr. Lynn Banowsky was the next head of the transplant program until Dr. Andy Novick who had trained under Dr. Straffon became chief in 1985.
Dr. Magnus Magnusson who started training under me in 1967 became staff in 1971. He established one of the country’s best pioneer organ perfusion laboratories using Dr. Fred Belzerʼs technique designed to evaluate and preserve cadaveric kidneys for transplantation.11 Dr. Emil Paganini who received training under me became head of dialysis section in 1985. In pathology, Dr. Sharad Deodhar became the transplant pathologist, succeeding Dr. Senhauser. Dr. Deodhar who was also one of the earliest clinical immunopathologist recognized the need for a tissue typing specialist. He recruited Dr. William Braun from the transplant program at Brigham in 1968. He trained at Dr. Paul Terasakiʼs laboratory at UCLA and established a tissue typing laboratory at CCF. Drs. Straffon and I stepped down in 1989 and Dr. Novick and Dr. Braun took over the program.
Last but not least, certainly deserving special recognition are the residents who served under Dr. Kolff from 1956 to 1967 and then under me. They were Drs. Sergio Acchardo, Fredrick Brown, Nancy Barber, Werner Bauditz, Claude Beaudry, George Dunea, Julio Figueroa, Birman Khastagir, Mark Kramer, Juan Ocon, Kathryn Popowniak, Dudley Seto, Masakatu Shibagaki, Arthur Shimizu, and Earl Smith. They were on duty 24/7 doing emergency dialysis and/or procuring deceased donor kidneys at CCF as well as from other regional hospitals.
On October 17, 2013, the Departments of Urology and Nephrology celebrated CCFʼs 50th anniversary of kidney transplants. Dr. David Goldfarb who is the head of kidney transplantation at the Department of Urology was the master of ceremonies. He pointed out that more than 3,000 transplants have been performed at CCF over a 50-year period. More than 75 patients have lived with the same functioning grafts for 30~40 years, and about 45 of those patients are still alive with the same functioning allografts. In 2013, CCF performed 184 kidney transplants, the most done in any single year.
Satoru Nakamoto was born in Yamaguchi, Japan in 1927. After having received his medical degree at Yamaguchi Medical School in Yamaguchi, Japan, he held intern and residency positions in Hawaii, New York City, Denver, and Cleveland, OH, USA. He served as a full staff at the Cleveland Clinic Foundation from 1961 until his retirement in 1991.