May 1954: the first ever symposium on the artificial kidney

Giovanni B. Fogazzi

Divisione di Nefrologia, Ospedale Maggiore, IRCCS, Milano, Italy

Correspondence and offprint requests to: Giovanni B. Fogazzi, Divisione di Nefrologia, Ospedale Maggiore, IRCCS, Via Commenda 15, 20122 Milano, Italy. Email: fogazzi{at}policlinico.mi.it

Introduction

‘The first symposium on the artificial kidney’ took place on May 1 and 2, 1954, in Rapallo, a nice little town on the Riviera near Genoa, Italy. This was the first meeting organized on the subject not only in Italy and Europe, but most probably also throughout the whole world. It represents today an important ‘historical probe’, which allows us to penetrate and analyse all aspects concerning the use of the artificial kidney in the early 1950s.

This paper describes the main aspects of the symposium, but omits some details concerning the names of delegates, and facts of only local importance. These may be of interest to Italian readers, but would be of little interest for those outside Italy. However, a fuller and detailed account—in Italian—can be found in a recent issue of Giornale Italiano di Nefrologia [1].

Symposium outline

The symposium was organized by Vittorio Pettinari (1901–1967), Professor of Surgical Pathology at Padua, and Luigi Stropeni (1885–1962), Professor of Surgery at Genoa, who were the chiefs of the two Italian groups with the greatest experience in the field of the artificial kidney.

The invited participants were all the Italians with an expertise in this area, and also three experts from abroad: the Spanish urologist Louis Bartrina Soler (1903–1974) from Barcelona, and the French physicians Marcel Legrain (b. 1923) and George Pinard. The latter two were members of the group of the Hôtel Dieu hospital in Paris, directed by Maurice Dérot (1901–1985), which at that time had one of the largest experiences in the use of artificial kidneys in Europe. Altogether there were 36 delegates, and all the Italians, with a few exceptions, were general surgeons or urologists, several of whom had built an artificial kidney of their own design.

The programme of the symposium included three sections, the first of which was on ‘extracorporeal circulation’, the second on ‘haemodialysis’ and the third on ‘clinical aspects and organization’.

Each section included several contributions, each of which was followed by a discussion. All contributions and discussions were recorded by dictaphone, transcribed and collected in the proceedings of the symposium. These were published in the same year as the symposium as a supplement of more than 100 pages to a surgical journal, which is no longer published [2].

Topics discussed during the Symposium

Choice between open-fractionated and closed-continuous dialysis
Open-fractionated dialysis had been used first by Georg Haas (1886–1971) in 1925–1927, and to begin with by Willem Kolff (b. 1911) in 1943. Here the technique was supported only by Bartrina [3,4]. It consisted of taking from the patient 400–500 ml of blood made non-coagulable by the addition of sodium citrate, and transferring this blood to a ‘dialysing cell’. This consisted of a narrow cavity bound by two membranes of cellulose acetate whose sides measured 20 cm. The cell was then placed for a variable time (usually only 1 or 2 h) in a container filled with the dialysis fluid. The procedure could be repeated several times in the same patient and was much simpler than closed dialysis, and above all avoided systemic coagulation. However, the open-fractioned system was not very efficient, and most speakers during the symposium maintained that they preferred the closed-continuous system, whose principle is the same as that which we use today (i.e. circulation of the patient’s blood through an extracorporeal system including a dialyser, and return to the patient’s circulation again).

Arterial rather than venous access for blood
With some types of artificial kidneys, among which was the rotating drum model designed by Willem Kolff, the blood was usually taken through an artery and returned through a vein, although veno-venous dialysis was also performed. In this case, the flow of the blood through the dialyser was sustained by the heart and the rotation of the blood in the tubing on the horizontal drum, which could result in cardio-vascular instability and/or inefficient dialysis. For these reasons, most speakers were in favour of a venous access for both the aspiration and return of the blood. This approach, however, required the use of two pumps to sustain and regulate the blood flow through the dialyser.

Type of dialysis membrane
At that time, cellulose acetate (‘cellophane’) was the membrane for artificial kidneys. Cellophane could be tubular or in sheets, according to the type of artificial kidney used. When tubular, it was wound in a spiral around a cylinder, and could be of variable length and diameter. No cellophane of good quality was produced in Italy, so everybody bought it from Visking Corporation of Chicago, which was the leading company of the time.

The use of heparin
As today, heparin was needed to prevent clotting in the extracorporeal system. In the early 1950s, its use was very much feared, especially in the event that a patient submitted to an artificial kidney should need an urgent surgical operation. However, during the symposium, it was stressed that, thanks to the elimination from the extracorporeal system of metal and rough surfaces, and the coating of glass components and connections with silicon, the doses of heparin could be greatly reduced. In addition, it had become known by that time that heparin effects could be neutralized by the use of protamine sulfate. For these reasons, this substance began to be administered at the end of each dialysis session, even in the absence of any major bleeding.

Reactions to pyrogenic substances
These reactions were very frequent, and were characterized by terrible shiverings, high fever and acute hypotension. These symptoms could be prevented partially by proper cleaning of the equipment and by boiling the cellophane to eliminate impurities. This was a long procedure, however, which could take 12 h or more. In addition, after boiling, the integrity of the cellophane had to be checked by visual inspection and by pumping of air into it, manoeuvres which could cause new contamination and new risks of reactions.

Acute hypotension
This also was frequent during dialysis in the early days. In addition to the boiling of cellophane, this could be prevented in part by a strict regulation of the volume of blood taken from, and returned to, the patient. This, however, was often a difficult task, due to the high and unstable volume of blood circulating in the various systems, which was favoured by the distensibility of the cellophane. This problem was especially evident in the rotating-drum dialyser of Kolff.

Nature of dialysis
The discussion about the nature of uraemia and the substances which could be removed by dialysis was long and detailed. The view was supported that the artificial kidney not only ‘cleaned’ the blood, but also provided a ‘re-balancing’ action on the interstitial compartment, whilst its action at the intracellular level was almost totally unknown.

How to evaluate the efficacy of the artificial kidney was also discussed at length. ‘Extraction index’, ‘dialysis index’ and ‘the measurement of clearances’ were all discussed and considered to be useful and reliable methods. The participants were unaware of Wolf’s mathematical analysis of urea exchange during dialysis, published that same year in the USA, which has formed the basis for assessement of the quantity of dialysis ever since.

Dialysis fluid
Most speakers had already noted that a better blood dialysis exchange could be obtained if the dialysis fluid circulated countercurrent to the blood stream and with a high flux. In addition, it had become known that it was possible to increase water extraction by adding to the dialysis fluid osmotic compounds such as polyvinylpyrrolidone (PVP), or the less expensive glucose. The composition of the dialysis fluid could thus be varied, and for this reason the artificial kidney started being seen as a ‘dynamic method’, which could be adapted to the patient’s situation.

Indications for the use of the artificial kidney
In the early 1950s, the artificial kidney was considered as a treatment only for patients affected by potentially reversible renal failure, and during the symposium nobody went beyond this view. Artificial kidney treatment was indicated in acute anurias of whatever cause, in acute deterioration of function in chronic renal disease, and for some poisonings. Much less clear was the utility of the artificial kidney in acute renal failure associated with burns, while its use in haemodynamic overload conditions was still seen as ‘a problem of the future’.

Moreover, there was plenty of uncertainty about how to judge which patient should be dialysed and which not. The only certainty in this respect, which the speakers had derived mostly from unhappy personal experience, was that it was not to be used ‘in dying or hopeless patients’, for whom haemodialysis would have only worsened an already irreversible situation. Very prudently, therefore, a speaker recommended "a judiciously early use of the artificial kidney, convinced as we are today that we are not doing any damage".

Because of these uncertainties, several speakers reminded the audience that the artificial kidney was not the only means to correct uraemia, and that several other interventional methods were possible, all simple when compared with treatment with the artificial kidney (Table 1). In addition, it was felt that the use of an artificial kidney could lead to the neglect of traditional procedures of ‘proven utility’. Among these, one of the most popular amongst surgeons and urologists was renal decapsulation, which had been popularized by the American George Edebohls (1853–1908) in the early 1900s [5] and was in vogue for half a century. However, it was now at the end of its period of use, as data had shown that it at best did nothing to improve the patients, and might well injure them.


View this table:
[in this window]
[in a new window]
 
Table 1. Techniques alternative to the artificial kidney which were used in the treatment of acute renal failure in the early 1950s

 
Organization
During the symposium, it became clear that the use of the artificial kidney was possible only through the formation of specialized teams and well-trained personnel, who could intervene with skill and rapidity in emergency situations, as cases with acute renal failure often were. Without such features being in place, the use of the artificial kidney could be either difficult or impossible. In addition, use of the artificial kidney also needed a laboratory in which a number of biochemical measurements (urea, electrolytes, glucose, pH for both blood and dialysis fluid, haematocrit) could be done rapidly and reliably. This was a very crucial problem, since in Italy in 1954 laboratories with such features were available only in Genoa and Padua.

Historical context

Background to the first symposium on the artificial kidney
The symposium took place several years after the introduction of modern practical artificial kidneys using heparin and cellophane in the 1940s by the physician Willem Kolff (b. 1911) in The Netherlands, the surgeon Gordon Murray (1894–1976) in the USA, and the physician Nils Alwall (1906–1986) in Sweden. It also came after the artificial kidney had been introduced, for occasional or regular use, in several other European countries such as the UK (in 1946–1948, but abandoned until 1957), Spain (in 1949 through Bartrina, but again abandoned until 1951), France (1949 onwards) and in Germany (1950 onwards) [6]. As far as Italy was concerned, the symposium came only 2 years after the first artificial kidneys of local production had been put in use in vitro and in animal experiments [1], and only 1 year after the first published report of their use in humans [7].

When the symposium took place, the organizers were well aware of the fact that it was the first in Italy and Europe on the subject [2]. Interestingly, today we know that it was the first ever meeting on the artificial kidney, since the first American meeting on this topic was held in 1955 at the initiative of the American Society for Artificial Internal Organs (ASAIO) [8].

The symposium was also among the very few meetings devoted to a renal subject after the end of the Second World War. In fact, in Europe, before it took place, there had been only the meetings of the Société de Pathologie Rénale, founded in 1949, which were held twice a year in Paris [9], and the meetings of the British Renal Association. The latter began in 1950, and its activities at that time climaxed in the international meeting on ‘The Kidney’, which was held in London in 1953 [10]. Renal meetings were also scanty in the USA where, since 1949, only the annual meetings of the National Nephrosis Foundation, an annual meeting on renal failure, took place, and the informal ‘salt and water club’, which was based in New England and met from time to time.

An interesting historical question is why the symposium happened to be organized in Italy rather than in another European country. Probably it was because in Italy interest in the artificial kidney was, from the very beginning, widespread. In fact, when the symposium took place, there were no less than 13 individuals working in seven different centres, which were spread all over the country, who had constructed or used an artificial kidney. This is a remarkable figure, and the number of individuals working on the artifical kidney in Italy in 1954 equalled—and may even have exceeded—all those working in all the other countries of Europe at that time; in Spain and the UK, there was no-one at all doing such work, and only a handful in France, Germany, Scandinavia, and individuals in one or two countries in Central Europe.

Did the symposium have any impact in and outside Italy?
In order to answer this question, I have interviewed several Italians who attended the meeting [11] as well as Marcel Legrain [12]. All of them today have almost completely forgotten the symposium! This is reasonable after almost 50 years, and especially when one considers that most of those who attended had shifted from the artificial kidney to other clinical interests during their subsequent careers. Thus, I can only hypothesize that at the time, the symposium provided the delegates with an update about the state of the art on the artificial kidney, but without going beyond this limited influence.

As to a possible impact outside Italy, it can easily be answered that the symposium had no influence whatsoever. This was due mainly to the fact that the proceedings of the symposium were published in an Italian language journal, with a limited circulation. This was a typical feature of the Italian scientific literature of the period, in spite of contributions which were often as good or as original as those published abroad, as has been demonstrated with the early use of percutaneous renal biopsy [13] and several other nephrological activities [14]. At a time when the languages of medicine were English and to a lesser extent French, the publication of papers only in the Italian language hampered the diffusion of interesting results abroad. In addition, in the early 1950s, Italy was an isolated country in the context of Europe also as a consequence of the outcome of the Second World War. At that time, the world had barriers to travel and communication which are difficult to appreciate today, and the interaction between countries was far less intense than it is now.

Prominent involvement of surgeons and urologists
We have seen that the symposium had been organized by two surgeons, and that the delegates were, with few exceptions, surgeons or urologists. This feature was typical of several countries (such as Japan), even though in Italy it was particularly prominent.

This could have several explanations. One is, at that time, anuric patients usually ended up in surgical or urological wards rather than in medical wards, a consequence of the fact that only with invasive surgical procedures, such as retrograde pyelography or nephrostomy, was it possible to distinguish a medical from an obstructive anuria. Therefore, it was only natural that surgeons and urologists became interested in a technique which could save the life of patients they saw quite frequently in their wards, and for whom they often had rather ineffective treatments.

Furthermore, before industry entered the field of haemodialysis, anyone wanting to start work with an artificial kidney had to design and build their own machine from scratch. This required a rather practical and even manual approach to the problem, a feature which is more typical of surgeons’ work than physicians’. Indeed, artificial kidneys in the early years also required a great deal of manual work to be put in use. This included the preparation of the cellophane, its mounting in the machine (which was probably the most tedious and time-consuming manoeuvre), the preparation of dialysis fluid, and the surgical isolation and cannulation of vessels.

Another possible reason for the prominent involvement of surgeons may have been the strong scepticism of physicians towards the use of the artificial kidney. I have not been able to document this attitude in Italy, neither in papers nor in interviews. However, this may have been a factor, as it was in other countries, in which influential physicians such as the Briton Graham Bull (1918–1987), the Dutchman J. Gerd Borst (1902–1975), and the Americans John P. Peters (1887–1956) and Arthur Grollman (1900–1976) strongly opposed the use of the artificial kidney, preferring to use some form of ‘conservative treatment’ [6]. This consisted of strict limitation of fluid intake and the administration of high energy diets, or of anabolic steroids to limit the catabolism and reduce blood urea and potassium.

In Italy, in spite of the fact that a co-operation between surgeons and physicians in the field started as early as 1956 with Antonio Vercellone (1923–2000) in Turin [1], it was only in the 1960s that physicians, under the appearance of nephrologists, took over the leading role.

Difficulties and pitfalls
The symposium shows us all the difficulties which were associated with the use of the artificial kidney in the early 1950s. First of all, there were technical difficulties, and these were of two types. On the one hand, there were difficulties (e.g. the correct use of heparin or the means to reduce the reaction to pyrogenic substances) for which solutions were already at hand, and which could be used to guide everyday practice. On the other hand, there still were problems difficult to resolve, such as the lack of availability of adequate laboratories for the measurement of metabolites and electrolytes, and the lack of well trained teams.

Technical difficulties drove conceptual limitations, the greatest of which concerned the indications for an artificial kidney. In spite of the long debate developed during the symposium, the only clear-cut indication for artificial kidney treatment remained the patient with reversible acute renal failure, provided his general condition was not too compromised. Other indications such as the use of an artificial kidney in fluid overload conditions, however stunning it may appear today, were still in the future. In this respect, in Italy, we had to wait until 1966 to have a report which clearly demonstrated the utility of the artificial kidney in the treatment of pulmonary oedema in uraemic patients [15].

Successes
In spite of everything, the artificial kidney appeared to be a good treatment already during the symposium. First of all, it began to be perceived as a technique which, when used in the proper way, would do little or no damage to the patient. Then it started becoming clear that it could be a ‘dynamic tool’, which could be adapted to the conditions of the patient, a feature which is still pursued today. Finally, the symposium showed that even amongst many doubts and many failures, there were a few patients who had survived thanks to it—two patients described in Italy by the time the symposium took place [2,16]. These rare successes, for patients for whom acute renal failure would have meant almost certain death, were extremely important not only for the patients themselves but also because they stimulated further attempts and developments, which led to the haemodialysis treatment we know today.

Conclusions

The symposium described here shows all the doubts, failures and the few successes which were encountered in the early years in one of the branches which contributed a great deal to the founding of our subspecialty. An important lesson worth learning is that our present efforts will appear as imperfect as those of the past in the eyes of future investigators.

Acknowledgments

The author is grateful to the editor of the Historical Notes, Professor J. Stewart Cameron, for his constructive criticism and advice during the preparation of the present paper.

Conflict of interest statement. None declared.

References

  1. Fogazzi GB. L’ introduzione del rene artificiale in Italia. G Ital Nefrol 2002; 19: 658–671[Medline]
  2. Pettinari V (a cura di). Atti I symposium sul rene artificiale. Rapallo 1–2 maggio 1954. Chir Patol Sperim 1954; 2 [Suppl 2]: 1–107
  3. Bartrina L. Riñon artificial. Nuevo aparato y nueva técnica. Med Clin Barcelona 1950; 8: 398–403
  4. Bartrina L. Experiencias sobre mi riñón artificial. Minerva Urol 1951; 3: 134–135
  5. Edebhols GM. The Surgical Treatment of Bright’s Disease. Lisiecki, New York, NY, 1904
  6. Cameron JS. History of Treatment of Renal Failure by Dialysis. Oxford University Press, Oxford, UK, 2002
  7. Battezzati M, Taddei C, Scarsi GM. Il rene artificiale. Considerazioni sull’applicazione nell’uomo della dialisi extracorporea. Min Med 1953; 44: 2010–2015
  8. Doolan P. Letter to the author. 26th November, 2002
  9. Richet G. La Société de Pathologie Rénale (1948–1959). Néphrologie 2000; 21: 23–26[ISI][Medline]
  10. Cameron JS. The First Half Century of the Renal Association 1950–2000. Renal Association, London, UK, 2000
  11. The persons interviewed were: Mariano Milost Della Grazia (who introduced the artificial kidney in Milan), Ludovico Ramoino and Vincenzo Bachi (who worked in Genoa with Mario Battezzati and Carlo Taddei, who were the first to use an artificial kidney in Italy)
  12. Legrain M. Letter to the author. 21st November, 2002
  13. Fogazzi GB, Cameron JS. The early introduction of renal biopsy in Italy. Kidney Int 1999; 56: 1951–1961[CrossRef][ISI][Medline]
  14. Richet G, Traeger J, Cameron JS et al. La nascita e lo sviluppo della nefrologia italiana moderna visti da Parigi, Lione, e Londra. G Ital Nefrol 2001; 18: 458–468
  15. Cerulli N, Bruscagli G, De Vita F et al. L’emodialisi nell’edema polmonare acuto dell’uremico. Atti IX Congrès Union Thérapeutique Internationale, Salsomaggiore Terme, 14–16 Aprile 1966; I: 321–322
  16. Confortini P, Siracusano F, Guerra A et al. Rene artificiale. Primi studi clinici. Boll Soc Triv Chir 1954; 8: 1–4
  17. Fieschi A, Baldini M. Fisiopatologia degli Stati Uremici. Edizioni Scientifiche Italiane, Napoli: 1953: 160–261




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Fogazzi, G. B.
PubMed
PubMed Citation
Articles by Fogazzi, G. B.