Renal Therapy in Lund: Homage to Dr. Nils Alwall
Dr. Horst KlinkmannMay 13, 1997
Dr. Klinkmann Horst Klinkmann, M.D.
Dr. Klinkmann is currently Professor of Medicine at the University of Glasgow, Scotland, and Director of the International Faculty in Artificial Organs of the International Society of Artificial Organs.
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Dr. Bengt Rippe:
And now the next presentation is by Professor Horst Klinkmann, who is one of the real pioneers who worked with Professor Alwall in the 1950s and who is former Professor in Rostock and presently with the International Faculty of Artificial Organs, and he's traveling a lot. So when I asked him what position he has, he said, "Just say that I'm in Chair #87 on a SAS or Lufthansa flight." It is a very great pleasure to call upon Professor Klinkmann. The title of his presentation is "Renal Therapy in Lund: Homage to Dr. Nils Alwall."
Mrs. Alwall, the daughter of Nils, Professor Rippe, Professor Bergström. Carl Kjellstrand for 35 years has told me what to do, though he has set the stage ever since we started to be the residents of Nils Alwall here in Lund. It is always a difficult job to follow Carl, but it is also a pleasure to cover a period which specifically is important for this area, for the world, and that once again illustrates how Lund has contributed with the group of Nils Alwall to the development of medicine in general and specifically in dialysis.
A very special time period: 1947 - 1965:
Between 1947 and 1965 more than 30 papers entitled on the artificial kidney appeared in Acta Medica Scandinavica describing the discoveries and development of a group of enthusiasts, of which I see a few here among us, and I am specifically pleased to see Per Erlanson, Carl Eric Hagstam, Birger Lindergard, all of us who have been together for almost half of a life. But also it shows that the time when I was with Nils Alwall, in 1965, Nils followed his basic idea that science and research always had to be combined with practical use and to be transferred into industry. I found, looking through my own personal archives, this article in Arbeitet, which was probably the first founding article of that company with the famous blue and white design that is now based here in Lund (Gambro). This is the time (period) that I'm going to cover in the following 30 minutes.
A telegram to Lund from London in 1948:
As Carl has told you, Ladies and Gentlemen, the history of dialysis sees Nils Alwall in the middle, together with Pim Kolff, the other great guy I had the privilege to work with. It also shows you in this German slide -- it's an original Nils Alwall slide which he prepared for the German Society of Internal Medicine (All of the slides that I am going to use are slides which were made together with Nils.) -- In 1948, for the first time, the development in Lund got international recognition when this telegram from London came to Lund asking if the artificial kidney developed here in Lund in 1948 would be available for treatment in London. So when Carl showed you that science disappeared after the war, international relations got re-established, and this historic document shows the first international recognition of the work of Nils Alwall.
The key contributions in the development of dialysis:
I put together what, in my opinion, are the eight most important contributions in literature in the development of the artificial kidney, starting with Thomas Graham's work; Abel, Roundtree, and Turner; going over my countryman, Georg Haas; to Nils Alwall on the artificial kidney and apparatus for dialysis of blood in vivo in the Acta Medica Scandinavica in 1947; and then finishing with Belding Scribner's work, who as we'll see later on, was influenced by Nils' work quite considerably.
The thick, green book:
I am showing you also another book which is thick, green, and very difficult to read. Most of us have worked on this book: Therapeutic and Diagnostic Problems in Severe Renal Failure. It comprises the work of Alwall, describing very meticulously every individual patient he had treated at that time.
Dr. Alwall's pioneering use of the renal biopsy:
But I also have to remind us that probably Professor Alwall has been the very first one performing renal biopsy, one thing that has been forgotten for a long time. And if you look at that paper published by him, the present author seems to have been the first to use percutaneous renal biopsy.
Improving the Kolff artificial kidney: a housing that permitted ultrafiltration:
Most of us are not aware that Nils Alwall started off as a pharmacologist with a lot of interest in physiology. Before moving to the artificial kidney, his overall interest was more the pharmacology and physiology of renal diseases, than the mechanical machine. However that year, in 1947, you see the old Kolff kidney here. You'll see immediately the difference. The Kolff kidney, being without any housing, with the cellophane wrapped around here, and one of the first experimental designs of Nils Alwall shows the progress of that design. It shows clearly that with this kidney you have the housing that enables you to do ultrafiltration. So clearly enough, the original contribution is ultrafiltration, and overhydration as part of uremic toxicity has always been the interest of Professor Nils Alwall.
Role of Nils Alwall in conceiving of the arteriovenous shunt:
Another original invention that sometimes is attributed to somebody else is shown here in the original drawings from 1948: It is the arterial-venous shunt. Firstly used by Alwall in rabbits, drawn here, connecting the carotid (artery) and the jugular vein. Using first the now again modern approach of using our collar veins, but also in 1948 he already drew an arterial venous shunt used in the lower extremities. This has been recognized by Belding Scribner several times in his lectures, that the idea of the arterial venous shunt was somehow given to him also by Alwall when he performed it. I still remember, and Carl and Per, you will recall, the times when we were really furious having to use these glass cannulas to put in and then trying to make those glass cannulas ourselves for building the arteriovenous shunt, one thing that has been forgotten in history for quite some time.
An atmosphere of skepticism:
Nils was tireless developing his apparatus and his machine. You see here in 1946, the device of that machine, which among several of us we could not count how many different designs he had in mind and how many he really performed. But he experienced also in Lund, some skepticism -- and how should I say it -- conservatism, of established medicine; he experienced some constraints by his peers.
The first Chair in Nephrology in Lund:
It took until 1957, when he received a personal Chair of Nephrology by the King (that he was recognized). I looked through the international literature; (this was) probably the first ever Chair of Nephrology given anywhere in the world. So at Lund University, Professor Rippe, you are keeping the first Chair of Nephrology (established) in the world. The other contribution is that also from here, from this Chair on, the first specialty of nephrology emerged, and the first specialized nephrologists also were based at Lund University. We always forget that machine contributions, technical devices, of course, are putting big progress into medicine. But organization, background, and education are still prevailing. I think in this respect, Alwall has been one of our front runners.
Alwall's visit to Seattle in 1963:
I still recall his pictures, which he brought back from Scribner when he visited for the first time Belding Scribner in 1963, bringing back these two pictures with Clyde Shields, one of the famous, long-lasting dialysis patients, and his first fistula, which can be seen here, or the first Quinton-Scribner shunt put in here. But at the same time, he came home not only impressed by the work that was going on in Seattle but also somehow depressed by the committee that was established there, which decided who lives, who dies -- this was a very much talked about committee at that time in Seattle, selecting patients to continue to be allowed to live or not.
And also, as you can see here, at the same time he published that it would be possible now in the 60s to make tremendous progress in treating dialysis, which we have seen from Carl's excellent lecture to us today, after the long time of development, though future approaches were here.
Then he found in the surrounding area, in Avesta, the first manufacturer of the long-lasting artificial kidney, which we hated because we had to prepare it, we had to wind the cellophane around here and then put it in here, and then found out that they were leaking and had to take it out again. Well at least it was a physical exercise; and if you see the machine-like establishment here, which we used those days to prepare the dialysate, you know how much mechanical and technical progress has been gone on.
Nils Alwall's emphasis on uremic fluid overload:
However, at that time, Nils Alwall became more and more concerned about what he termed "uremic fluid-retention, lung." I think it is the first time in literature that ultra-filtration had been used and over-hydration had somehow been added to the uremic toxicity. If you look at the table where he listed all these patients, you will see how many of them had been dying from edema, fluid retention lung and overhydration. We have been taught by him to look at the overhydration as one of the most important parts of uremic toxicity. Therefore, I think we really can count that the first hemofiltration treatment ever reported is in that green book, being performed by Alwall on this patient; and sequential ultrafiltration, which later on was really brought into clinical practice by Jonas Bergström, was used first here in nephrotic syndrome patients, just to remove fluid. At that time, it was a pioneering approach because edema in itself was not considered to be really part of uremia. His physiology and pharmacology background resulted in these early steps of real pioneering work.
The formation of Gambro Inc.
He, Nils, was a restless researcher, sometimes shy in his personal life, but aggressive if he was going to pursue his ideas, and this is when he met Holger Crawfoord. The merger... and how should I say... combination of the businessman, having been successful in Sweden, and the researcher, who was looking for somebody to finance his work, finally resulted in the construction of one of the first small-plate dialyzers that later on became the basis of industrial development and which was shown in the first article in Arbeitet.
The Professor and his pupils
However, in these days, which we all remember very well, Nils was extremely nervous. He was locking himself up all the time, he wasn't available for us, and we got a little bit tired sometimes. So Carl Kjellstrand and myself, sitting in the same room in 1964, put up a big sign on our desk saying: "Every professor above 50 should be poisoned." Carl, I hope I am allowed to show this. When Carl and I turned 50, both of us had a small telephone conversation, and we agreed to postpone that time a little bit. The reason, however, was Nils Alwall, in our opinion, followed August Bierce's maxim: "The Professor is also a gentleman who is always of a different opinion." I'm not going to elaborate on this any more. I leave you with this. But, again, it shows that a teacher has to cause some counter-reaction by his pupils in order to be remembered.
Emphasis on various body spaces and disequilibrium
Nils Alwall was, and he never, never denied this, always a physiologist. This is another of the old pictures where he tried to teach us about the differences between extracellular and intracellular (spaces). He has been one of the very first to tell us that dialysis is not only detoxification, but also dehydration -- one of his biggest contributions. It (dialysis) is also disequilibrium between the different body spaces, and finally, it is depletion. And this is still something which I believe some parts of the world where we have low-life expectancy and high mortality should remember -- that modeling requires two or at least three- pool modeling in order to fulfill physiological requirements. I am thankful to my teacher, Nils Alwall, that he enabled me to do my Ph.D. in the late 1960s, pointing out the uremic disequilibrium syndrome, where urea protects against the cerebrospinal fluid all the time and if you do a very short, very efficient dialysis, immediately in cerebrospinal fluid, the urea level there gets to be higher than in the blood, the osmotic pressure rises, and the patient develops cerebral edema. Today we see this as a rise in blood pressure for which, I believe, a very basic physiological explanation has been given here. It is probably more important than questions of biocompatibility or any of the modern things. If you dialyze your patients using sessions that are long enough, you keep them well. That is the message that we had been told in the early 60s by Nils Alwall, which has a tendency to be forgotten.
Uremic toxicity has always been the focus of his attention. This is a slide from 1963--muscle-wasting, bone disease, polyneuropathy, central nervous system disorders, hormonal dysregulation, and so on, and fluid overload was described. And I believe there is not so much difference up until today. And if you read the description in one of Alwall's papers of what he considers uremia to be, it is a description that I think without any discussion could be used today as it was written about 35 years ago.
Nils Alwall and Tore Lindholm
It is a sad occasion, but I think that we should remember that one of his young and early collaborators, who was going with Nils and who always kept the balance of being the doctor in the group of Nils, was our mutual friend Totte Lindholm, who untimely disappeared before he could participate in this session with us. Without Totte being the counterbalance to Nils, also in a political way (I remember several furious talks with different political opinions on the marketplace between the two) -- without Totte, I think, things might have gone differently, and we should be grateful for his contribution.
Role in organizing systems of dialysis providers
Ladies and Gentleman, another basic interest of Nils was the organization of dialysis: hemodialysis, being organized in this way, into a program as well in treatment and manufacturing. It shows clearly the two main points which have always been prevailing in Alwall's work in Lund. He was already, as I pointed out, concerned about short-time individualization of treatment. There was a question of center dialysis, which was preferred. Home and satellite was just an idea which came. But he also warned, and a strong warning should be put up, that you cannot just use this machine -- you do have to have education. With his strong warning of the need for education, I think he is also one of the pioneers who put nephrology up as a specific educational area needing training into the consciousness of his peers.
Role in organizing dialysis registries
Another point which needs to be recalled is the first ever given survey of a dialysis population was published in 1965 when Nils put together data from 35 dialysis centers in Eastern Europe and Northern Europe and Sweden, publishing for the first time the total number, as you can see here from 1946 until 1964, where hemodialysis had 99 percent prevalence and peritoneal dialysis only 1 percent. But more interesting, at this time, acute cases were 70 percent of the total; chronic cases only amounted to 30 percent. This work of Alwall finally became the basis for putting together the EDTA Registry, the oldest and first registry in the world. Basically the ideal for registries came from Lund, from Nils.
Nils Alwall's influence in Hungary
Where did his ideas flow to? They flowed behind the Iron Curtain. He, having been specifically attached to Hungary because he spent a year in Pécs in the Pharmaceutical Institute, he gave his idea, and this was the first-ever constructed artificial kidney in Eastern Europe, constructed in a place called Hódmezõvásárhely Kutasi Puszta, in Hungary. It looks like a Hódmezõvásárhely Kutasi Puszta. It was about 2 tons heavy, but you can clearly see it is basically similar, encased here and wrapped around, an Alwall artificial kidney in salami style. I also believe that you can see here the only picture where it has been possible to bring those two together: Pim Kolff and Nils Alwall. This was the only picture taken so far, the only time they met was on a boat in Berlin on a river cruise.
So, with that, Ladies and Gentleman, I have to emotionally pay my respect to Nils. When he gave his last international talk in Chicago at the 5th World Congress of the ISAO, frail but happy. And he pointed out to us that pioneering work only will reflect on human beings if it is able to go to everybody. And if you will recall, today access to dialysis therapy in the world population is only 25 percent, I think we have a lot to do to fulfill the mission of these remarkable men. Nils Alwall was a true pioneer. He was the first to perform percutaneous renal biopsy. He was the first who designed a dialyzer with controllable ultrafiltration. He probably is the father of the arterial venous shunt. He was the first appointed Professor of Nephrology in the world. Also, he laid the basis for the dialysis registry. This is probably too much for one man.
Nils Alwall was a scientist. He was, in a way, a politician. I remember him as being personally shy, being very aggressive, living for his family, being aggressive as it runs to the protection of his patients. It is a fulfilled life, Ladies and Gentlemen, but at this time we have a mission to fulfill and I am happy that Lund University and Swedish Nephrology is carrying on this mission.
Thank you very much.
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