Originally published in Volume 36 Issue 4 of Artificial Organs, 10 April 2012
Real dialysis pioneers, such as John Jacob Abel, Geog Haas, Willem Johan Kolff, Nils Alwall, Georg Ganter, Arnold M. Seligman, Howard A. Frank, Jacob Fine, and others, are all deceased by now, but I may consider myself as a next generation of early users and developers of some new ideas in dialysis.
I graduated from the Medical Academy in Kraków, Poland in 1959. Internal medicine was strong in Kraków at that time, particularly hematology in the II Department of Internal Diseases under the chairmanship of Prof. Tadeusz Tempka (1885–1974), who introduced bone marrow biopsy and coagulology. I wanted to be an internist with subspecialty in hematology; unfortunately, there was no position for me, so I started to work as a volunteer at this Department, but took a paid position in the Emergency Medicine.
My volunteer work counted also as residency for specialization in internal medicine. In 1961, Dr. Przemysław Hirszel, who was an intern in the Department at that time, and I received good news: Doc. Zygmunt Hanicki was able to get permission to open a dialysis center in the Department. There would be positions for physicians in a newly built artificial kidney unit. The opening was scheduled for the fall of 1962, but we were supposed to study hard in the new field and be ready before the deadline. We agreed immediately as it appeared to be something fascinating and completely new to us. Besides, I would be paid for my work in the Department, whereas a position in hematology was not available. I had never heard about the artificial kidney during my 5 years in medical school. There were some subspecialties of internal medicine, but nephrology did not exist in Poland at that time. Doc. Hanicki gave us reprints of the numerous papers of Nils Alwall, as the department was supposed to get Alwall’s kidney. We were also supposed to help in the final stages of room remodeling and machine assemblage. To become acquainted with the procedure, we were sent for a few days to the Artificial Kidney Center at the Warsaw Medical Academy in Poland, where they had used Alwall’s kidney for the treatment of acute renal failure since January 1959. The best instructor for us was Dr. Zbigniew Fałda.
Our unit was supposed to be opened in September 1962; however, on Monday, June 11, a young patient with oliguric acute renal failure was admitted to the Department and Doc. Hanicki decided to perform dialysis, if possible, as no artificial kidney center (at the time, there were three: in Poznań, Warsaw, and Lódź) was able to admit him and the patient might die without dialysis. Dr. Hirszel and I were supposed to inspect the adaptation of the rooms and all equipment. The spiral dialyzer of Nils Alwall consisted of two metal cylinders (inner and outer), a 140-L tank, where the assembled metal cylinders were contained, and a huge 700-L tank located in the adjacent room, high above the floor. Dialysis solution was prepared in the huge tank and transferred through a hose to the 140-L tank. There were additional parts, like cellophane and latex tubing, glass cylinders, blood pump (sigma or finger pump), a glass bubble catcher, and a manometer. Water softener was needed for the preparation of the dialysis solution, and a gas bottle with carbogen was also present. In 2 days, everything was ready. The patient’s uremic syndrome deteriorated, so the decision was made that the dialysis had to be performed before the weekend and was set for Friday, June 15, 1962. I was supposed to assemble the dialyzer and prepare the dialysis solution. Dr. Hirszel was supposed to make sure that all the ingredients for the dialysis solutions were prepared by our pharmacy and that the water softener was ready to use.
I started to prepare the dialyzer early on Thursday expecting some glitches. And there indeed were glitches. I inserted the glass cylinder into the latex tubing and tied cellophane tubing to the latex, with a string, and then I wrapped the cellophane tubing on the inner cylinder, inserted the latex tubing with the glass cylinder into the cellophane on the other end, and tied them with a string. This was done on a special support with the cylinder in a horizontal position. Then I put the cylinder in an upright position, took the outer cylinder, and placed it over the inner cylinder. This had to be done very carefully, as any deviation from the ideal direction could damage the cellophane tubing. Some centers had a hoist to help with this maneuver; we did not, so I relied on my strength to do it right. Then I placed the assembled dialyzer into the tank filled with water. The next step was to attach a manometer to the upper latex tubing and pump air into the lower latex tubing. The cellophane tubing was supposed to tolerate over 150 mm Hg of pressure. I was very disappointed when I saw air bubbles coming from several places. I tried to localize them as carefully as I could, because their location would indicate to me where the jagged areas were. I disassembled the dialyzer and started to look for spikes. They were very tiny, therefore difficult to feel with fingers. I found a few of them and removed them with my wife’s fingernail file. I had to repeat the process four times until I assembled the dialyzer capable of withstanding 150 mm Hg of air pressure. Then I tried to boil water in the tank. It was not without difficulty as the steam pressure was low. Ultimately, I got enough steam to the dialysis room and finally the dialyzer was sterilized. I filled the huge tank with 700 L of softened water and heated it to 39°C (102.2°F). I also attached a hose to the carbogen tank and bubbled it through the water. It was now about seven in the morning on Friday, June 15, 1962. As a final preparation, Dr. Hirszel put all the ingredients already prepared by the pharmacy into the water. I also checked whether all the ingredients were added in proper amounts (double check for this step was absolutely necessary), and we mixed them with a huge, wooden spade. Then, we drained the water from the 140-L tank, filled it with dialysis solution, and attached a hose with carbogen to keep the solution pH level below 7.4. The tank was covered with a plastic lid provided with a heater, thermometer, and mixing blades.
We started the finger pump and filled the dialyzer with 1 L of donor blood. Dr. Hirszel inserted the polyethylene cannulae of the Fałda-Deczkowski shunt. We connected them with latex tubing, injected heparin into the venous line, and started the dialysis. The dialysis was complicated by clot formation, fluctuations of blood pressure related to high dialyzer capacity, and patient’s “bleeding” into the dialyzer with any increase of outflow pressure. Ultimately, we were able to finish the 6-h dialysis session. It was an exhausting procedure. The patient was dialyzed two more times, regained his renal function, and was discharged from the hospital within 4 weeks and lived for many years thereafter. In retrospect, we were convinced that the patient would have died without dialysis, so all our efforts were absolutely necessary and rewarding. There were no more dialysis sessions performed until after the official opening of the Artificial Kidney Unit on August 01, 1962. Dr. Hirszel and I filled the positions and I stopped working in Emergency Medicine as of September 1962.
The problems we encountered during the first dialysis, especially with blood pressure, influenced me profoundly. I thought that with this kind of dialyzer, the future of dialysis was not very bright. The only hope was that the usually bulky machines would be reduced in size and their services simplified. The most important issue for me was the reduction of dialyzer capacity without reducing dialysis efficiency. I theorized that it would be ideal to have a capacity of less than 250 mL, so there would be no need for donor blood and “bleeding” into the dialyzer with increased outflow resistance. I ended up thinking about this issue almost constantly. I read about other dialyzers manufactured at that time; they did not appear optimal to me. The solution came to me suddenly as I was falling asleep at eleven o’clock on Sunday, November 11, 1962. I awoke with the thought that a capillary artificial kidney should maintain high efficiency with low internal capacity. The implications of this realization were profound; if I made a dialyzer from capillaries instead of larger tubes, then its capacity would be lower while maintaining a high surface area. This concept was patented in 1964 1, but I was unable to build such a dialyzer in Poland. I published the theoretical consideration of an ideal dialyzer and provided detailed calculation methods of dialysis efficiencies for “capillary” dialyzers with different capacities, surface areas, and membrane thicknesses 2. This concept was a basis of my PhD thesis. When I met Dr. Richard Stewart during the Annual Dialysis Conference in Seattle on March 02, 2003, he told me that he was not aware of my publication for several years. He admitted that using my calculations, it would have taken them markedly less time to come up with the clinically useful capillary kidney described in 1968 3.
In 1963, Doc. Hanicki told Dr. Hirszel and me that the Ministry of Mining decided to buy an artificial kidney, as they were disappointed with the treatment of miners with crush syndrome so common in victims of roof collapse in a mine gallery. They requested the opening of the IV Department of Internal Medicine with an artificial kidney center in the Hospital for Miners, in Bytom. Doc. Hanicki asked us to coordinate the process, make sure that all parts were delivered and the dialysis room was properly constructed, and ensure that physicians and nurses were trained. He was supposed to come and direct the center when it was ready. The Ministry of Mining had more financial resources to buy better dialysis equipment. We suggested not buying Alwall’s kidney, as there were new machines available. We suggested buying a tank system with coil dialyzers from Fischer-Freiburg, in West Germany.
We were ready in the middle of 1964 and we expected that Doc. Hanicki would come soon. It was a surprise when we learned that he changed his mind. I was offered a position of interim chairman of the Department and Dialysis Unit as there was no other candidate. I was only 30 at that time so I was scared, but the situation forced me to learn faster. My years in Bytom were very productive. I introduced prophylactic dialysis in hypercatabolic acute renal failure (like in crush syndrome). Shortly thereafter, we started chronic hemodialysis and kidney transplants. With our technique of frequent and long hemodialysis sessions, we had no mortality in patients with chronic renal failure. There was no way to admit more patients. It was extremely difficult as there was constant pressure to accept new patients to our program. At some point, I was desperate and pondered what would be my best approach in solving this problem. Should I admit everybody and dialyze with short and infrequent dialyses, accepting a high mortality rate, or should I dialyze the best way I could determine and restrict the number of admissions? The first approach was absolutely unacceptable, as it would contradict the aim of treatment, that is, prolongation of useful patient life. I came to the conclusion that it is better to dialyze as well as possible to show authorities that the method is good and deserves development and support. Although it was emotionally difficult for me to reject new candidates, I was deeply convinced that this had to be our approach. The medical criteria for admission were rather straightforward: the patient had to be between the ages of 20 and 50 and have primary renal disease (no systemic disease). I tried to establish a committee to enforce criteria (similar to the Death and Life Committee in Seattle), but I did not have any candidates willing to serve, and when I learned that the Seattle Committee was disbanded, I ceased trying. The selection of patients for chronic dialysis was the most difficult problem for me during all the time I worked in Poland.
As one solution to the problem, we started a chronic intermittent peritoneal dialysis program in the center and at home, but the results were worse than those with hemodialysis, particularly in patients with low residual renal function. A better answer to the problem of selection would have been expanding the chronic hemodialysis program, but that would not have been an easy task as there were no funds for such an endeavor. Fortunately, it happened that in our outpatient clinic, we were following a young lady with chronic glomerulonephritis who was a daughter of a prominent official in the Ministry of Mining. It was obvious that she would need chronic dialysis in 1971 at the latest. I told her father that I had all spaces occupied. He offered to provide resources for new kidney machines and remodel our dialysis center if we would consider taking his daughter into the program. The work on remodeling started, and we received five Travenol RSP kidney machines. However, there was an obstacle to utilizing our unit at full capacity. Our Department of Health, which was supposed to provide dialyzers, told us that we would get only 1200 Ultra-Flow 145 dialyzers per year. It was obvious that if we wanted to use all our machines at full capacity, we would perform at least 3000 dialyses per year. As a result, we started to work hard on a dialyzer reuse method. We modified the method of Pollard et al. for Kiil dialyzers by using only tap water and 2% formaldehyde for rinsing dialyzers. The dialyzers with arterial and venous lines were kept in canisters with 2% formaldehyde in between dialysis sessions. To increase the number of reuses, we decided to weld the whole mesh at the bottom to prevent telescoping of the dialyzer. Our method of reuse was patented (Polish patent Nr 74 878 filed February 07, 1972, granted May 30, 1973).
Since 1969, I wanted to determine the best way of dialysis. In all patients treated from March 1969 to May 1973, the amount (duration and frequency) of dialysis sessions was adjusted to eradicate all symptoms and signs of uremia and achieve full rehabilitation. The results of these studies were published in three papers 4–6. The most important conclusions were that more frequent and longer dialyses gave better clinical and laboratory results. In patients with diuresis below 500 mL/day, a minimum frequency and duration on coil dialyzers, with dialyzer blood flow of 200 ml/min and dialyzate flow of 500 ml/min, should be three times weekly for 8 or 9 h. Some patients required four times for 6 or 7 h or 5 h 5–6 times weekly. Longer and more frequent dialysis had beneficial effect on dry body weight, hematocrit, serum albumin concentration, blood pressure control, and nerve conduction velocity. This study was the basis of my habilitation thesis. Prof. Franciszek Kokot was my patron for the habilitation procedure.
Protein losses during peritoneal dialysis were considered to be a major obstacle for the widespread use of chronic peritoneal dialysis. We observed that some patients did not show any decrease in serum protein after months of peritoneal dialysis. The most important observation in our studies was that there were individual differences in protein losses. This observation inclined me to think that the transport rates of other substances may vary in individual patients, and it was the basis of my later studies on the peritoneal equilibration test.
The last important observation in Bytom was that insertion of needles into the arteriovenous fistula in the same site was beneficial for decreased rates of hematoma and pseudoaneurysm formation and overall fistula survival 7. This method, later renamed the buttonhole method of fistula cannulation, is widely used particularly in home hemodialysis.
Since 1981, I worked in Columbia, MO, USA with Dr. Karl D. Nolph and Dr. Ramesh Khanna. At that time, dialysis was already well established, but still some new methods could be developed. My contributions were: peritoneal equilibration test 8 for determination of the most suitable dialysis technique in patients, high volume exchanges 9, nightly intermittent peritoneal dialysis, and tidal peritoneal dialysis 10. I also worked on peritoneal access and developed a swan neck peritoneal catheter (US patent 4 687 471) and a presternal peritoneal catheter (US patent 5 171 227). Both were manufactured by the Accurate Surgical Instruments in Toronto, Canada. The most widely used access has been the Palindrome intravenous catheter for hemodialysis manufactured by Covidien Company based on my patents (5 569 182; 5 685 867; 5 961 486). This catheter does not have blood recirculation with either direction of blood flow during hemodialysis, hence the name Palindrome.
Another important contribution to the development of hemodialysis technology was a machine for frequent hemodialysis (Patents 5 336 165; 5 484 397; 5 902 476; 6 132 616; and 6 146 536). This machine was built by AKSYS Ltd. and had several important features. First of all, the machine reused dialyzers and lines to decrease the cost. Second, it prepared dialysis solution from dry chemicals. Third, the machine prepared itself automatically for dialysis to save the patient’s time. The third feature made the machine “user friendly” and easy to learn and use, and made a helper not essential. The details of the machine were described in an invited editorial 11. AKSYS ceased operating in 2007 and the patents were acquired by Baxter Company, and a new, improved version of the machine was developed in 2011.
Zbylut J. Twardowski, MD, PhD, Professor Emeritus of Medicine, a native of Poland, coorganized dialysis centers in Kraków, Poland, and Bytom, Poland. He is a founding member of the Polish Society of Nephrology, International Society of Peritoneal Dialysis, and International Society of Hemodialysis. He was the Founding Editor of Hemodialysis International. His major contributions to improvement in the technique of dialysis included the theoretical basis of ideal (capillary) dialyzer, buttonhole method of needle insertion into arteriovenous fistula, determination of the beneficial effects of longer and more frequent hemodialyses, peritoneal equilibration test and several offshoots of peritoneal dialysis, improved catheters for peritoneal dialysis, palindrome intravenous catheter for hemodialysis, and machine for frequent home hemodialysis. Dr. Twardowski is an honorary member of many nephrology societies, and received the American Kidney Fund Torchbearer Award and ISHD Belding Scribner Trailblazer Award.