Nils Alwall – one of precursors of dialysis treatment

Abstract

Nils Alwall (1904-1986) came from a small village in southern Sweden. In 1923 he began his medical studies at the Lund University, to graduate in 1932. During his studies he conducted experimental work and in 1935 defended his doctoral thesis in pharmacology. In 1936 he was awarded the title of associate professor of pharmacology and started clinical practice combined with experimental research in the Department of Medicine at Lund. In 1940 Alwall obtained the position of assistant professor of practical medicine and in 1957 was promoted to professor of nephrology at the world’s first Department of Nephrology. His medical interests were many-sided but mostly related to kidney diseases and replacement therapy after the loss of renal function. From 1941 he worked on the construction of the vertical drum artificial kidney, tested mostly in rabbits, which also enabled ultrafiltration. The dialysis was first applied in September 1946 in a patient with severe uremia, and soon afterwards the first ward for artificial kidney therapy was established. Thenceforward Lund department became the leading center for treatment of acute and later also chronic renal insufficiency. Alwall was also the inventor of the arteriovenous shunt (1943-1948) and the pioneer in the use of renal biopsy (1943). He also inspired creation of the Gambro Company in Lund (1964) which resulted in construction of coil dialyzer (1966) and sheet single-use plate dialyzer (1967). Alwall was also involved in the founding of the International Society of Nephrology (1960), European Dialysis and Transplant Association (1964), and Swedish Society of Nephrology (1964), engaged at leading positions in these organizations, also after his retirement in 1971. He is an author and coauthor of 203 publications.

 

Keywords: Nils Alwall, Dialysis Treatment, artificial kidney

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Introduction

In the early 1940s three pioneers independently created artificial kidney apparatuses and applied them for treatment of renal failure. These pioneers were Willem Kolff (The Netherlands), Nils Alwall (Sweden) and Gordon Murray (Canada). Nils Alwall, (Figure 1) began experiments with dialysis in animals, mainly rabbits, in the early 1940s. Willem Kolff made similar attempts in patients since 1943. They first made contact in 1946. Alwall performed the first dialysis in a patient in September 1946 and Murray did that three months later. Earlier they both performed repeated animal experiments which actually delayed clinical attempts but contributed to a later success in subjects (1).

 

Nils Alwall – early education and young physician (2, 3)

He was born in October 7, 1904 as Nils Andersson in a small village (Figure 2) in southern Sweden. After public school his further education was supported by a childless uncle Jons. Already in the high school (where he had chosen a humanistic class with Greek and Latin) he was taking interest in technical aspects of the surrounding world and showed a gift of leadership. In 1923 he graduated from the high school, completed education at mathematics, physics and chemistry courses and in December the same year began medical studies at the University of Lund. He was active in the students’ federation, served as a secretary and executive vice-chairman. In the health-promoting committee he implemented measures aimed at prevention and treatment of tuberculosis which was common at the time among medical students. Among other things, Nils arranged periodical radiological and ESR check-up sessions and reserved for convalescent students forty low-cost beds (25 US cents daily) in a nearby sanatorium. Nils took also an active part in organization of periodical students’ festivities (Swedish “carnivals”), the profits were used to supplement the sanatorium’s library. As an appreciated orator he was often invited to deliver an occasional speech. The summers of 1924 and 1925 he spent on army training in a medical unit, obtained driving license, and enjoyed riding a military motorcycle. With time, in 1942, he was promoted to the rank of captain in the medical units.

During the second year of his studies Nils became particularly interested in physiology and professor Torsten Thunberg offered him the assistant position, without salary but ensuring free accomodation at the attics of the Institute of Physiology. Nils stayed there for nearly four hard years, continuing his medical studies, conducting classes with students and engaging in his own experimental work. In 1927 Nils and his brother Edvin decided to change their family name from Andersson (regarded too common) to Alwall. In 1928 he published the results of the first experimental work, on the method of determination of dehydrogenase in rabbit blood. A year later he obtained the post of assistant at the Institute of Pharmacology, as before without payment, but with the privilege of free accommodation in a laboratory room and also access to experimental animals. Then he began his doctoral study on the role of dinitrophenol as a factor enhancing metabolism (and weight loss) in rabbits. After an internship in clinical departments (including one of obstetrics and gynecology where he had handled 50 deliveries), in the spring of 1932 he became a qualified doctor and started his work as a general practitioner in small villages in southern Sweden until 1934 (with annual salary of US $ 450). At the same time he continued his work on the doctoral thesis, which he defended in 1935. At the promotional ceremony of new doctors he delivered a speech in Latin, without using any written text. Afterwards he left for Pecs in Hungary, on invitation from his friend Geza Mansfeld, and there acquainted himself with experimental research with dogs. After return from Hungary he was appointed an associate professor in pharmacology, and in the autumn 1936 started his career in the Medical Clinic, University of Lund. Between 1928 and 1937 Nils Alwall published 17 articles, mostly experimental studies. However his interest focused increasingly on the clinical work. Although heavily burdened by the everyday clinical duties (up to 70 hours per week) he found time to play football, and took part in the university annual match: associated professors against the team of the vice-chairman of the student federation.

 

The dream of the artificial kidney (3, 4)

At that time the treatment of patients with renal failure symptoms and edema was confined to low protein diet and almost prone positioning in bed, sometimes for many months. Nils was extremely moved by poor, if any, results of such treatment. This feeling of helplessness must have given rise to the idea of a need for a radical help, such as creation of an apparatus replacing the function of the damaged kidney – artificial kidney (AK). Alwall was then responsible for a 57-bed internal medicine ward and for teaching medical students; his position was assistant professor of practical medicine. Fortunately, new premises to accommodate small animals (rabbits) had been opened in the Clinic’s basement and in 1941 he received a regular scholarship for associate professor (US $ 1,400 per year) so he could devote a part of time to experiments with AK. They were performed usually after finished work at internal ward as to not disturb the patient’s care. In 1941-42 his experimental apparatus resembled the later introduced flat-plate dialyzer (dialysis filter). These results were never published because Alwall felt that the approach was not practical.

The next models of AK had a shape of a vertical drum of different sizes used in experiments since 1942 (Figure 3). After a single procedure the blood urea level was reduced by 20 to 30%, repeated dialysis could significantly prolong the animal’s life. Until 1953 almost 2000 rabbits were used in different experiments.

Glass cannulae and a small rubber tubes were used to get access to the artery and vein before the each dialysis and removed after the procedure. After several procedures vessels were damaged and further treatment was not possible. Repeated dialysis treatment required a more sophisticated approach and Alwall developed an arteriovenous shunt. Using already available heparin, patency of the arteriovenous shunts could be prolonged up to one week and maximally 7 dialyses in the same animal could be performed. These experiments with arteriovenous shunts were published in 1949 (5). This method of access to the vascular system was also used in patients but was later abandoned because of clotting and development of infection (6). The materials used were too primitive to obtain better results of shunts patency. Belding Scribner discussed with Alwall the problems with arteriovenous shunt in 1954, and visited Alwall’s Clinic in 1958; there is no doubt that they talked at length about the shunts. Scribner came to Lund again after the Congress in Geneva in 1960 (where he presented a new Quinton-Scribner shunt using PTFE – Teflon tubing) and brought a coil of a new material (Teflon) as a gift to Alwall.

In 1943-44 Alwall applied percutaneous renal biopsy (the first in the world) using the Iversen and Roholm needle for liver biopsy (7). Biopsy material was sucked into a syringe and sent for microscopic examination in Copenhagen. Alwall performed 13 renal biopsies but, unfortunately, the last patient went into shock, probably due to a reaction to the contrast medium, developed acute renal failure and died. After that Alwall discontinued the biopsies until 1950s. A report on all kidney biopsies done during the year 1943-44 was published in 1952 (8).

Modified and larger models of AK, suitable for use in large animals (dogs) and in patients were created in the workshops of the Institute of Physiology. Alwall covered the costs of production from his own pocket. In 1946 he received a grant of US $ 800 and could hire two assistants to help with animal experiments. This support was crucial for further investments required for improvement of the AK.

Alwall was prepared to carry out dialysis treatment in patients already in 1944. However, the head of the medical clinic, even though favorably disposed to the Alwall’s ideas, advocated patience and waiting for suitable circumstances. It was feared that the death of a patient during treatment would prevent the approval by the central health authorities of the entire dialysis program. In addition, the local colleagues were opposed to Alwall’s ideas and were reluctant to send the patients for dialysis treatment which they considered as very dangerous procedure.

 

Coming to clinical dialysis

At last it happened that an unconscious patient with terminal chronic renal failure and pneumonia was sent to the clinic from another hospital. The dialysis procedure was performed in the laboratory room on the night of 3/4 September 1946, it lasted 6 hours. The patient’s condition and the biochemical parameters improved: blood urea level decreased by 98 mg% to 320 mg% (53 mmoL/L), approx. 45 g of urea has been removed from the body (Figure 4). However, the general condition was critical from the very beginning and he died of respiratory failure on the next day. Nevertheless, Alwall’s later conclusion was that this promising result of the dialysis procedure was a turning point on the way to implementation of this method of treatment in Lund (4).

Soon afterwards Alwall received US $ 1000 to adapt facilities in the clinic to the requirements of dialysis procedures. By December 1946 the construction of this world’s first dialysis department with a total area of 26 m2 was completed. It consisted of two rooms, where one AK apparatus and a 100 L water tank were installed. In January 1947 dialysis treatment was used in the second patient, who survived further 15 years, and in February the same year the third patient was treated. These three cases were presented in a publication in the same year (9).

Throughout his work at the Institute of Physiology Alwall took great interest in the mechanism of edema formation. He thought that also overhydration is responsible for the symptoms of uremia. Therefore quite early Alwall explored the possibility of applying dialysis to remove excess of water from the body (ultrafiltration, UF). At first in rabbits overhydrated 115% and later in patients he achieved significant UF by creating positive pressure in the extracorporeal blood channel or negative pressure in the dialysis fluid. In this way an UF of about 0,3 – 1,0 L/hour could be obtained. No other AK available at that time offered such possibility. Quite often Alwall’s patients urgently needed UF because of pulmonary edema (called by him “uremic lungs”), often secondary to the recommended Borst’s diet which involved fluid overload in anuric patients. To avoid complications (connected with blood pressure fall) during UF, since 1949 Alwall ordered strict control of bed-weight throughout the period of treatment and a special bed scale was constructed (6). Beginning from 1950 radiological chest control was performed frequently, sometimes every day. The weight of the patients hospitalized in the clinic was monitored daily. To the guests visiting the Alwall’s clinic the emphasis on the status of hydration of patients, especially during the dialysis treatment, was a major novelty.

Because of the increasing demand for AK, Alwall started the production of apparatuses made of hard rubber (ebonite), in cooperation with the rubber factory. These constructions were suitable to perform UF by creating negative pressure in the dialysate during dialysis procedure in rabbits and were used in patients between 1947 and 1949. However, they did not withstand steam sterilization and gradually underwent deformation. Therefore Alwall started cooperation with the steel factory in the town Avesta and AK made of stainless steel (Avesta model) were used since 1949 (3, 4). Subsequent models (altogether about 50 apparatuses were produced) underwent various modifications and were sold by Avesta factory to 17 countries in 1950s. By the end of 1960s they were still used in more than 40 dialysis centers in the world. The interest for dialysis treatment increased greatly after publication of 8 cases of dialyzed patients in Lancet in 1948 (10) (Figure 5). The Clinic in Lund attracted attention worldwide and soon increasing number of doctors were coming to visit and take training. In 1948 Alwall was invited to London and Vienna with his staff and his apparatus to perform dialysis treatment in patients not suitable for transport to Sweden. In 1949 his annual salary was increased to US $ 4,000.

In the subsequent year 1950 the dialysis department was expanded by addition of another room and the second AK was added. The preparation room was equipped with a big steam sterilizer and a large tank for the dialysate, 800 liters in capacity. Tap water was passed through the columns of a softener. Alwall already used the dialysate with reduced sodium chloride concentration at that time. As for the early 1950s these were extremely modern facilities and John Merrill, when on visit to Lund, called them “hotel class”.

Since 1954 in the guest book of the Clinic more than 450 inscriptions have accumulated, by visitors and trainee doctors from more than 40 countries of all continents. Alwall was also invited to various medical centers around the world to lecture on dialysis. He took part in many scientific congresses and symposia.

Alwall believed that the methods of therapy current at the time: appropriate diet and bed rest, should be combined in selected cases with dialysis treatment. His contemporary colleagues were skeptical about such dialysis treatment in patients with renal failure but Alwall obtained unexpected support from surgeons who had to deal with many cases of postoperative acute renal failure, especially in the field of oral, abdominal and vascular surgery which ruled out the use of dietary treatment. There were also many cases of toxic kidney damage secondary to treatment with antibiotics. Many of these patients were transferred to Alwall’s clinic and dialysis treatment was applied in all such cases, including the patients on artificial ventilation (appropriate ventilator machine had been installed in the dialysis department). Not surprisingly, initially the mortality was very high so that instead of saying ” the dialysed patient died” the expression “the patient was “alwalled” was ironically used. Later, in the middle 1950s, the results of dialysis treatment were much better owing to the earlier admission to the dialysis department, before patient’s condition became critical, and this saying was abandoned. Alwall reported restoration of renal function after about 80 days of dialysis treatment. This was in discordance with the opinion that after 2 weeks the treatment of patients with anuria should be abandoned.

In 1949 Alwall performed the pioneering experiment of hemofiltration in a uremic rabbit, 2.1 kg in weight. During the 6-hours’ procedure 700 ml of fluid was removed and compensated by intravenous administration of electrolyte solution. For such treatment Alwall used the term of “exchangeable UF” and noticed that it gave a similar effect as dialysis (11). In 1952 he published the results of exchangeable UF treatment of barbiturate poisoning in rabbits. Suicide by barbiturate poisoning was frequent in the years 1940–1950 and in patients with barbiturate poisoning Alwall, as the first in the world, used dialysis treatment (12). Spectacular responses were observed with patients having come out of coma after dialysis and asking for a cup of coffee. In 1952 Alwall published a case of a recovery from excessive resistant edema in a patient with nephrotic syndrome and normal renal function. Strong diuretics were not available at that time. Over the period of 6 weeks Alwall performed three UF sessions without dialysis (called later isolated UF) and removed about 30 liters of edema fluid without compromising renal function (6, 11). His idea of hemofiltration was introduced by Lee Henderson into treatment of uremia in patients in 1967 and idea of isolated UF was introduced by Jonas Bergström into the clinic in 1976. In 1950 Alwall described also, as one of the first authors in the world, the clinical picture of diabetic nephropathy, and diabetic nephropathy in the absence of diabetes mellitus (13). Alwall was also the first clinician to draw attention to the nephrotoxicity of radiographic contrast media (14), in several cases he was forced to use dialysis treatment because of the so induced kidney function impairment.

The number of patients treated in Lund increased every year; they came from all over Sweden and from abroad. Initially, mainly the patients with acute renal failure were qualified for dialysis therapy however some patients with chronic renal failure were also treated. By 1961, 724 patients with acute renal failure and 351 with chronic renal failure (representing a 22% of all) had been treated with dialysis. A record survival rate in these chronic anuric cases was 186 days before Scribner’s shunt came to use (which gave an excellent testimony to the personal competence). In 1960 a regular dialysis program in patients with chronic renal failure was started in Lund and the requirement for disposable dialysis equipment became evident (3).

 

Toward kidney transplantation (2, 3)

In 1958 a tragical accident focused Swedish public opinion on the issue of kidney transplantation. A boy, 11 years of age, fell from a swing and suffered an injury of the kidney which had to be removed. It turned out that this was his sole kidney. Hemodialysis was started in Lund and the boy was sent with his parents to Boston for living donor kidney transplantation. Unfortunately, he died during immunosuppressive premedication before the operation. This happened when many authorities considered transplantation, not dialysis, an important approach in the treatment of renal failure. Alwall believed that application of the dialysis and transplantation must run in parallel; he was aware that transplantation program must be supported by dialysis treatment. Future transplant recipients had to be prepared for surgery and to have a possibility of further treatment after a possible loss of the transplant. Furthermore, he was sure that there would be problems with finding appropriate living donors and with availability of the cadaver kidneys for transplantation. All these considerations were expressed by Alwall very early, at the time when kidney transplantation was still in the starting phase.

In 1957 Alwall was appointed professor in nephrology (the first such position in the world) and thenceforward as a holder of the chair headed his own Department of Nephrology. He received funds for the expansion of the dialysis department, the area was then increased to 110 m2, there were 3 treatment rooms, each with an AK of Avesta. However, the need for dialysis treatment still exceeded the capacity of the Lund center. Until 1958 Alwall’s dialysis department was the only one in Sweden, thereafter new dialysis centers were opened in some large hospitals in Sweden but the demand was growing very fast, especially after 1966 when Cimino-Brescia arteriovenous fistula was introduced and a treatment program for patients with chronic renal failure was being implemented (15). Alwall actively tried to increase the refunding of dialysis treatment in Sweden, which resulted in a conflict at the ministerial level and in the medical community.

 

The disposable dialysis filter

In 1961 Nils Alwall met an industrialist Holger Crafoord. This man had made a long career in the management of the Åkerlund & Rausing and Tetra Pak Companies which introduced famous packaging system for fluids (Tetra Pak). Alwall talked about his work, dialysis patients, lack of proper equipment, technical problems and increasing demand for this kind of treatment in the world. Crafoord got fascinated by the Alwall’s story and based on mutual understanding the Gambro Company was founded in 1964. The name originated from the street Gamla Brogatan (Old Bridge Street) in Stockholm, where Crafoord was the owner of a dormant plant. As a result of collaboration with Alwall came the re-use coil dialysis filter (similar to the Kolff-Watschinger model) which was used in the years 1966-1967 (Figure 6). Then, in 1967, a fully disposable flat-plate dialyzer of Alwall’s type (Ad modum Alwall) was launched, the prototype weighed 7.5 kg. At this stage the construction team in Gambro was already numerous, consisted of people of various specialties and the Alwall’s role changed from that of a constructor to an investigator testing the new dialysis filters, providing comments and proposing amendments.

In 1968, the Department of Nephrology was moved to a new hospital building. The Clinical ward counted 42 beds, the dialysis department area was of about 1000 m2. There were 14 bed sites, each equipped with a Gambro dialysis monitor (AK1). This dialysis facility was at that time the world’s second in size and in terms of the number of treatments just after the Swedish Hospital in Seattle under Belding Scribner.

 

Family life, pensioner, promotor

Alwall’s family life started quite late, because he was too much occupied with daily work. It was not until 1941 when, at the age of 37, he met Ellen Alströmer a 14 years younger cousin of a colleague. Ellen was by education English philologist and psychologist. The wedding was the same year and the marriage lasted 45 years. They had 3 children (born 1943, 1944 and 1947). Ellen was a great support and help to her husband owing to her knowledge of foreign languages. She had completed her doctoral studies and was active in her profession.

Nils Alwall retired in 1971, in accordance with the Swedish regulations at the age of 67, and had been assigned a retirement office in the hospital. He was involved in didactic, journalistic and scientific activities until the middle 1980s. He was also leading a group working on the epidemiology of pyelonephritis and hypertension in the population of approx. 5000 people in Southern Sweden. Moreover, he worked as a consultant in nephrology in the outpatient clinic in Malmö in the years 1973-1984. He worked also as a legal representative of patients with kidney diseases and his interpellations regarding insurance and reimbursement of organ’s donor, covering of the dialysis costs for patients staying abroad, reimbursement of the family care costs, preventive health tests or providing treatment outside own province – had all been approved. In 1965 Alwall established the Museum of the History of Medicine at the University of Lund.

Alwall was politically engaged in Social Democratic Party health activities, at that time the ruling party in Sweden. During many years he was president of the Institute of Adult Education where periodically he held popular science lectures. He served as scientific adviser on nephrology and as a chairman in the committee for the need and organization of renal care in Sweden during many years. He was also involved in the creation of International Society of Nephrology (ISN, founded in 1960) where he held leading positions (vice-president, president-elect, president, past-president) in the years 1969-1981, and of the European Dialysis and Transplant Association (EDTA founded 1964), serving as member of the board (1964-1967) and president (1970-1971). He founded the Swedish Society of Nephrology (1964) and was its chairman (1964-1971). His efforts led to creation of an official subspecialty of kidney diseases in Sweden (1964). The idea of a registry of renal replacement therapy within the EDTA was based on the Alwall’s register from the years 1946-1964. At the inauguration of Gambro Laboratory in Lund (given the name of Alwall Laboratory) in January 1985 (Figure 7) he said: “I feel like a helmsman who has sailed to the shore and wishes the crew good luck in the further sailing.” The last public performance was as late as in October 1985 when he had a lecture on the history and development of dialysis at the ISAO congress in Chicago (16) and presented his own data from 1964 which had estimated the need for renal replacement therapy at a rate of 80 new patients/million population/year: this was close, to the present day estimations. A two months later he became ill, stopped driving the car. He arrived at the hospital where a young doctor wrote in Alwall’s chart: “he claims to be a retired professor of urology”. So short is public memory.

Alwall died suddenly the day after his admission, on February 2, 1986, of heart attack, and his ashes rest in the Lund cemetery. His last words to his bird-fan wife Ellen were: “Did you see the robin?”

 

Final remarks

Let us have a look backwards at the 72 years’ history of the development of dialysis treatment in medicine. Since the late 1970s there was an abrupt development of dialysis in the world. Strenuous Alwall’s efforts to increase the number of dialysis departments in Sweden (with present population of 9 million) led to opening of new dialysis units: 19 units with 98 dialysis sites were available in 1972, 32 units in 1982, and 65 units in 2016, with 4,000 patients with chronic renal failure treated with dialysis and another 5000 living with transplanted kidney. Especially in the early decades, the Alwall’s role was enormous: he was a doctor extremely devoted to patients, an organizer, designer, scientist, and social activist at the same time. Alwall believed that any treatment, also dialysis, should be equally accessible to everyone. This humanitarian approach could be observed in his relations with patients: their good was always of primary concern, and the same attitude was demanded of his subordinate doctors. He never gave up, even though the help in his activities offered by his contemporaries was rather limited. Quite often he had to struggle against negative opinions expressed by recognized experts in nephrology who were ill-disposed to his ideas, and also had to cope with financial limitations. He published, alone or together with his collaborators, 203 scientific papers, without counting those written in Swedish. To resume, he was a man endowed with a vision of the future regarding further development of dialysis and kidney transplantation. Nobody was able to foresee as well as did Alwall the growing incidence of chronic renal failure secondary to diabetes mellitus, hypertension, congestive heart disease, chronic vascular disease, application of contrast media and antibiotics and other drug toxicities. The lack of dialysis facilities was a shock to politicians controlling allocation of funds for the development of health service.
Nils Alwall was a prominent figure in nephrology and medicine, he educated generations of doctors, 31 physicians received the degree of doctor of medicine (17), not only those from internal medicine (nephrology) but also specialists in radiology, surgery, and infectious diseases. This illustrates the scale of the challenge to various fields of medicine in connection with kidney disease, and of the attempts to meet it. Thanks to his personal talents, entrepreneurship, hard work, determination and humanistic approach Alwall was able to effectively promote his idea and vision of the crucial role of dialysis in the treatment of patients with renal failure, and to open the way to kidney transplantation.

Thanks to his work, thousands of patients with kidney diseases have had longer and more dignified life. It was not surprising that in Sweden he was given the nickname of “Man of Miracle”.

 

References

  1. Cameron JS (2002) A history of the treatment of renal failure by dialysis. Oxford University Press, New York.
  2. Westling H (2000) Konstgjord njure. En bok om Nils Alwall. Atlantis, Stockholm.
  3. Alwall’s Archives in the Lund University Library.
  4. Alwall N (1984) Konstgjord njure – Babels torn. Sydsvenska Historiska Sällskapets Yearbook suppl. 4. Rahms, Lund.
  5. Alwall N, Bergsten BWB, Gedda PO, Norviit L, Steins AM (1949) On the artificial kidney IV. The technique in animal experiments. Acta Med Scand 132: 392-411.
  6. Alwall N (ed) (1963) Therapeutic and diagnostic problems in severe renal failure. Scandinavian University Books, Copenhagen, Stockholm, Oslo.
  7. Alwall N (1945) On percutaneous aspiration biopsy of the kidney. Contribution at a meeting of the Swedish Surgical Society in Lund, March 23rd
  8. Alwall N (1952) Aspiration biopsy of the kidney, including i.a. a report of a case diagnosed through aspiration biopsy of the kidney in 1944 and investigated at an autopsy 1950. Acta Med Scand 143: 430-435.
  9. Alwall N, Norviit L (1947) On artificial Kidney II. The effectivity of the apparatus. Acta Med Scand Suppl 196: 250-258.
  10. Alwall N, Norviit L, Steins AM (1948) Clinical extracorporeal dialysis of the blood with artificial kidney. Lancet issue 6489: 60-62.
  11. Alwall N (1979) Ultrafiltration and hemofiltration in 1940s and 1950s. Dial Transplant, 8: 535-6, 543
  12. Alwall N, Lindgren P, Lunderquist A (1952) On the artificial kidney XX. Treatment of severe phenobarbital poisoning in rabbits, by means of forced polyuria, exchange ultrafiltration and dialysis and a preliminary report on dialytic treatment of barbiturate poisoning in patients. Acta Med Scand 143: 299-306.
  13. Alwall N, Ekelund C, Oras L (1950) Intercapillary glomerulosclerosis. (Kimmelstiel-Wilson’s disease). Acta Med Scand 136: 359-370.
  14. Alwall N, Johnsson S, Tornberg A, Werkö L (1955) Acute renal failure following angiography. Especially the risk of repeated examination, revealed by eight cases (two deaths). Acta Chir Scand 109: 11-18.
  15. Kurkus J, Nykvist M, Lindergård B, Segelmark M (2007) Thirty-five years of hemodialysis: two case reports as a tribute to Nils Alwall. Am J Kidney Dis 42: 471-476.
  16. Alwall N (1985) Historical perspective on the development of artificial organs. The lecture from the Fifth World Congress of the ISAO in Chicago, October 6. Gambro AB Education Department, Sweden.
  17. Kjellstrand CM, Lindergård B, Odar-Cederlof I (2012) Nils Alwall, the first complete artificial kidney and the development of acute and chronic dialysis. p. 77-88. In: Todd SI, Rahman M, Kjellstrand CM (ed) Dialysis: History, Development and Promise. World Scientific Publishing Company, New Jersey.
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Nils Alwall and his input into the development of Polish haemodialysis

Abstract

Nils Alwall’s fame and reputation as a pioneer and leader of haemodialysis treatment of patients with chronic renal disease was widespread across Europe in the 1940s, 50s and 60s. Little wonder, then, that his renowned clinic in Lund, Sweden was willingly visited by many doctors from Central-Eastern Europe including those from Poland. The first Poles to meet Alwall in his native Sweden right after WW2 were Maria (nurse) and Bożysław (technical worker) Kurowski. The meeting gave rise to the publication of the first nursing paper in Poland in 1958. Nils Alwall’s archive in Lund holds rich correspondence exchanged with Polish doctors. The first one to establish contacts with the famous Swede was dr. Zygmunt Hanicki from Krakow, who later received one of Alwall’s first dialysis machines enabling him to perform experiments whose results were published in 1949 and 1950. The first longer stay in Lund started in 1957 when dr. Tadeusz Orłowski, the future leader of the Polish nephrology and transplant therapy, made his way to the famous centre. Next, in 1958 the clinic was visited by dr. Zdzisław Wiktor of Wrocław, the future Head of one of the first clinics of nephrology in Europe and the following year dr. Jan Roguski of Poznań also sought to gain experience there. In the meantime, a number of dialysis centres equipped with Alwall-type haemodialysis machines were set up in Poland including the Poznań unit (1958) established by Kazimierz Bączyk, the Warsaw one (1959) by Tadeusz Orłowski and the Krakow centre (1962) by Zygmunt Hanicki. It was in 1960 when dr. Zbigniew Fałda from Warsaw completed his training in Lund. Later, in 1966 the Lund centre hosted dr. Jan Kurkus. Nils Alwall’s first visit to Poland was in 1959 during the Congress of the Polish Society of Internal Medicine in Gdańsk. His second visit to Poland happened in 1970 when he gave two lectures. By the time Nils Alwall retired as many as a few dozen Polish doctors had gained experience in Lund later transplanting it to their centres in Poland confirming the significant impact of the Lund centre on the development of the Polish dialysis therapy.

Keywords: Nils Alwall, dialysis unit, Lund University, history of haemodialysis, Poland

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Introduction:

There can be little doubt that the introduction of haemodialysis into the treatment of patients with chronic renal disease was among the greatest medical achievements of the 20th century. In Europe, the pioneering investigations into the method began in the 1940s and were conducted independently by two outstanding figures – the Dutch Willem Kolff and the Swede Nils Alwall. Apparently, Poland was one of the first countries in post-war Europe which could have tapped into the advantages of the new method when one of the clinics of the Krakow Medical University received an early haemodialysis machine designed by Kolff, had it not been for the fact that most probably it was never used to treat patients. Alas, with Kolff’s interest being shifted to developing other artificial organs his cooperation with Polish doctors stopped. The other pioneer of the European dialysis treatment was Nils Alwall of Lund University in southern Sweden. It was him who in the 1940s, 1950s and 1960s had by far the largest experience in applying haemodialysis to treat patients with renal insufficiency using a self-designed machine. The first devices to be used in Poland, starting from 1958, came from Sweden and Alwall’s centre in Lund was the place where Polish doctors became acquainted with and gained experience in using this particular method of treatment (1- 3).

The history of Alwall’s contacts with Poles began right after the war when the Poznań-educated lawyer Bożysław Kurowski and his nurse wife Maria, both prisoners of German concentration camps, settled down in Sweden. The Polish couple worked at Alwall’s clinic since the early days of the newly-established dialysis centre. B. Kurowski’s job was as a technical assistant at the centre while his wife worked as a scientific assistant at the science and research laboratory. As such, both gained profound knowledge of the issues related to dialysis treatment. B. Kurowski was a co-author of a compendium titled Dialysis – the Tasks of Technical Assistants giving a detailed description of a machine preparation and testing as well as all the other activities necessary to run a dialysis session. As it was, Kurowski was Alwall’s right-hand man when it came to operating artificial kidneys. His wife, Maria, was the author of Artificial Kidney Saves Lives, a paper published in Pielęgniarka Polska in 1959 as one of the first publications on the subject in Poland. Owing to their linguistic skills, the Kurowskis were frequently asked by Alwall to introduce overseas visitors into technical intricacies of dialysis and their home would always be full of foreign guests including those from Poland who were having a training at Alwall’s clinic (4) (Figure 1).

The first letter from Poland to Alwall was sent on 12th March 1948 by dr. Zygmunt Hanicki from the 2nd Department of Internal Medicine at the Jagiellonian University in Krakow headed by professor Tadeusz Tempka. In his correspondence Hanicki enquired about technical details and the price of a dialysis machine. At the time, the new invention cost approx. 500-600 Swedish crowns, yet its production was a significantly long process. In order to go around this setback, Alwall’s idea was to lend an older-type machine, which had been used for performing dialysis in dogs, with which Hanicki could start experimenting. The size of the machine made it impossible to use it for human treatment. The organisational activities were troublesome and involved the Polish consulate in Stockholm, yet, finally, the machine arrived in Krakow in November 1948. The rich follow-up correspondence between Hanicki and Alwall, first in English and then in German, referred to the problems of starting the machine, dialysis clinical details or availability of heparin. The analysis of the letters exchanged by the two reveals that heparin was delivered to Krakow in December 1948, however, it remains unknown whether it was used for further experimental work with Alwall’s machine or not. In his early experiments, following in the footsteps of the famous Swede, Hanicki used sodium citrate as an anticoagulant. The letters unveil that Hanicki’s visit to Lund was also considered and discussed, however, it never happened. Instead, on 27th June 1949 he sent to Lund his first Polish publication on the work and application of the artificial kidney. In his subsequent publication, out in 1950, Hanicki presents the results of experimental dialyses with the use of aqueous urea solution and uremic patients’ blood. In July 1951 another piece of information about a planned visit to Lund appeared when Alwall issued a formal invitation for Hanicki to spend 6 weeks in his centre. Again, the visit never happened. In 1956, Hanicki informed Alwall about the fact that the Health Ministry had purchased three artificial kidneys from Avesta company which were to be delivered to the cities of Poznań, Warsaw and Krakow. It was the first information concerning the planned purchase of an artificial kidney for Krakow. We know that Andrzej Biernacki and Jan Roguski made significant efforts to ensure delivery of dialysis machines for Poznan and Warsaw respectively, which happened in 1958. Two years earlier, in February 1956, Hanicki made his way to Prague, Czechoslovakia to be trained with a machine that had already been installed there. In his last letter dated 29th January 1964 Hanicki reported that at the time there were as many as 5 artificial kidney centres, 3 of which used Avesta machines. Moreover, he informed that the Krakow centre had already been operating for one year and a half. Historical records show that it was opened in 1962 when the Warsaw and Poznań ones had already been in use. Later, Zygmunt Hanicki became Head of Clinic of Nephrology in Krakow. The correspondence between Alwall and Hanicki is among the most voluminous in the archive containing no fewer than 30 letters (5 – 8) (Figure 2).

Professor Stefan Wesołowski, a Warsaw-based urologist, met Alwall during a medical congress in Athens in April 1955. Two months later he sent a letter to Sweden asking Alwall if Wesołowski’s assistant, Tadeusz Krzeski, could pay a visit in Lund in order to learn about the artificial kidney. The answer was obviously positive and between 20th and 30th November 1956 Krzeski had a chance to get hands-on experience with the artificial kidney in Lund. It was the first documented visit of a Polish doctor at Alwall’s clinic. We know that later Krzeski remained faithful to his department of urology, Wesołowski, however, took part in Poland’s first peritoneal dialysis session performed in 1953 by Orłowski and Nielubowicz.

Tadeusz Orłowski, a Warsaw Medical University professor-to-be, met Nils Alwall in Geneva in October 1956, and then, in July 1957, sent a letter to Lund asking about a possibility to have a 2-month training there. The request was supported by a letter of recommendation provided by Andrzej Biernacki, the Head of the 1st Clinic of Internal Medicine in Warsaw. The visit, which was the first longer-time training of a Polish doctor in Lund, took place between 28th October and late December 1957. On his return to Poland, Orłowski shared the new knowledge and experience with his Polish colleagues at the clinic. Besides invaluable knowledge he also brought back new designs of catheters and of other necessary equipment, the value of which could not have been exaggerated for the clinic getting ready to obtain the first artificial kidney purchased by the Ministry of Health in mid-1958. The machine was first put to use to perform the first test dialysis in a dog on 31st December 1958. The first dialysis in a human patient happened only 2 days later, on 2nd January 1959 when a child was treated with the new method. A detailed account of the preparation process and the use of Alwall’s artificial kidney can be found in Zbigniew Fałda’s article. In subsequent years, Tadeusz Orłowski left the dialysis department to his assistants himself taking up the organisation of the renal transplant programme (9- 11) (Figure 3).

In his letter to Alwall dated 8th July 1958, professor Zdzisław Wiktor form the Wrocław Clinic of Nephrology asked the famous Swede about a possibility to have a training in Lund, which started on 10th December and lasted 2 weeks. The Clinic’s Guest Book contains an entry in German from 29th December 1958. In the next letter, Wiktor invited Alwall to come to Wrocław following the 20th Congress of Internal Medicine to be held in Gdańsk on 10-12 September 1959 which Alwall was going to attend. Alas, Alwall having to return to Lund, the visit never happened. Zdzisław Wiktor was the Head of Poland’s first and Europe’s one of the first clinics of nephrology established in 1958. The first haemodialysis in his centre was performed in 1964 (12, 13).

Jan Roguski from the 2nd Clinic of Internal Medicine at the Medical University of Poznań met Alwall during the Congress of Urology in Genoa in October 1956. In his letter dated 15th June 1957 he informed Alwall that the Ministry of Health had decided to purchase an artificial kidney from Sweden for the Poznań centre and asked the Swede to try and hasten the production and delivery of the machine. Alwall did intervene and promised that it would be made available within a few months, at the same time inviting one of the Poznań clinic’s doctors to Lund with an aim to provide training about the operation of the artificial kidney. Although dr. Kazimierz Bączyk was the one selected to visit Lund the lack of funds from the Ministry of Health made the trip impossible. Fortunately, Bączyk, who had already participated in a short training in Bern, Switzerland, possessed some knowledge and experience in using Alwall’s device. The artificial kidney, along with a batch of cellophane membrane, arrived in Poznań in mid-1958 and was first used in autumn that same year. The first haemodialysis session in Poland was performed in November 1958 by a team headed by Kazimierz Bączyk. Later, due to delayed deliveries from the USA, Roguski asks Alwall for help in obtaining cellophane membrane, a request which is eagerly granted. In January 1959 Roguski writes a letter in which he asks for an invitation to Lund for April in order to learn about the system of work at the clinic. However, the arrangement of the precise term of the visit will prove problematic due to Roguski’s planned trip to Philadelphia, USA in connection with Rockefeller Foundation Scholarship. Eventually, when he makes it to Lund on 2nd April 1959, Alwall is away giving lectures in Germany, Switzerland and Greece, so the two do not have a chance to meet. The first occasion to talk comes a few months later during the 20th Congress of Polish Internists held in Gdańsk on 10-12 September 1959 to which Alwall was officially invited by Roguski (14- 16).

One of the subjects discussed during the Congress was the treatment of advanced uraemia with the use of the artificial kidney, the method which had been used in Poland for the past 2 years. Alwall took an active part in the symposium talking especially about indications for dialysis and treatment results. With a whopping number of over 1000 sessions performed since 1946, the Lund clinic had enormous experience in the matter. Within the two preceding years (1957-1958) as many as 200 sessions were performed annually, which made it the leading haemodialysis centre in the world. The results of his observations were published by Alwall in the Polish Internal Medicine Archive in 1960 (17, 18).

In October 1959 Alwall received a letter from professor Antoni Horst which contained an invitation for Roguski’s 60th birthday and his 35th anniversary of scientific activity. The celebration was to be held in autumn 1960 and Alwall was requested to give a speech of his choice that would later be published in Polish Medical Journal. Finally, in 1960, the famous Swede prepared and published in Polish Doctors’ Weekly his paper titled On the Size of Kidneys in Acute Renal Failure (19) (Figure 4).

It was during the Congress of Internal Medicine in Gdańsk in September 1959 and, then, during his visit to the 1st Clinic of Internal Medicine in Warsaw that Alwall met Andrzej Biernacki and the clinic assistant Zbigniew Fałda who showed him around the Artificial Kidney Department. In his letter dated 10 February 1960 Fałda asked about a possibility to work at the Lund Dialysis Department for one month some time between May and August 1960. These being holiday months in Sweden when the clinic is usually short of staff and Alwall knowing about the Warsaw unit’s experience where 60 dialysis sessions had already been performed in patients combined with Fałda’s publications on technical problems with extracorporeal dialysis and his involvement in the creation of the film titled The Treatment of Acute Renal Failure with Alwall’s Artificial Kidney, permission was granted. Consequently, Fałda arrived in Lund on 31st May 1960 with disposable PVC venous catheters produced in cooperation with engineer Juliusz Deczkowski used in Warsaw since the late 1959. The catheters were put to test during dialysis sessions in Lund. Although Alwall himself was not present during the catheter implementation, later his comment was: “it works” and “it’s a good idea”. At that time glass cannulas and glass silicone-covered air-vents were used, little wonder, then, that Alwall was interested in replacing them with Fałda’s plastic catheters. On his return to Warsaw, Fałda sent to Lund about 100 catheters for further tests. Back in Sweden a young girl treated for 6 months with an initial diagnosis of acute renal failure caught Fałda’s attention. Anuria was still present, yet the general condition of the patient was good despite the unsolved problem with vascular access, which suggested remarkable skills of the dialysis team. Most probably, the acute renal failure had turned into the chronic one. Belding Scribner from Seattle, USA, started treating chronic renal failure a few months later (March 1960) using a new type of vascular access known as the Scribner’s shunt. However, amounting to 100 USD the cost of this facility was significant, which made it hardly affordable in Poland. Having returned from Lund Fałda had a similar idea and, in July 1960, he started working with Deczkowski with the aim to develop a Polish arteriovenous shunt based on widely-available polyethylene. Their shunt, which was later subject to gradual improvement, was successfully used at the Warsaw clinic to facilitate the process of treatment of acute renal failure. It was in August 1963 when Fałda gave a few arteriovenous shunts of his design to Alwall. Although he had already used Quinton shunts for the treatment of 15 patients he reportedly intended to use Fałda’s development at his clinic. That said, no clinical opinion was ever offered or published. Dr. Fałda’s impressions from his 1960 stay at the Lund clinic can be found in his two papers published in 1960 and 2010. The 1960s was a decade when more Polish doctors established contacts with Alwall and visited Lund and more papers on his artificial kidney were published (20- 23) (Figure 5, Figure 6).

Dr. Jerzy Wroński from the Miners Hospital in Bytom, Poland visited Nils Alwall in January 1962 after the hospital had put forward plans to open a dialysis unit. Wroński went to Sweden in order to learn about the technical details concerning the installation and operation of a dialysis machine, water quality as well as the general arrangement of dialysis facilities. Alwall’s response to these doubts was that a laboratory room should be arranged in a way that would enable transforming it into a dialysis room in the future, the size of which in turn should make it possible to fit in a ventilator. As regards water quality, it must be softened by means of special filters. The Bytom dialysis centre was opened in 1964, following efforts made by its organiser – Zbylut Twardowski, the future world-class nephrologist, author of numerous treatment-facilitating solutions for both HD and PD.

Jan Kurkus, the former assistant at the 1st Clinic of Internal Medicine in Warsaw, visited Alwall’s centre in September 1966 with a letter of recommendation from Tadeusz Orłowski, the Head of the Warsaw clinic, in his hand. The Swedish staff were more than kind and helpful towards the young Pole. During a two-hour conversation at Alwall’s office Kurkus had a chance to learn about the intricacies of the artificial kidney and was shown posters presenting growing trends of the numbers of patients in need of dialysis treatment in the years to come. The analysis of death certificates indicated that as many as 70 new patients per one million would appear each year, the level which was achieved in Sweden in the mid-1990s. It was during his stay in Lund that Jan Kurkus visited the Kurowskis for the first time, the acquaintance which was to change into a deep friendship with frequent almost family-like meetings. Kurkus’ second visit to Lund happened in 1969 following the ISN Congress in Stockholm when, accompanied by other workers form the 1st Clinic of Internal Medicine from Warsaw, he visited the newly-built Department of Nephrology and the Dialysis Centre with which, almost 26 years later, he was to be professionally tied.

The 1969 ISN Congress in Stockholm was preceded by Fałda’s request to Alwall concerning the participation of a group of doctors from Warsaw in the event and their intention to visit the Lund clinic afterwards. The visit of the group (Zbigniew Fałda, Hanna Fałda, Liliana Gradowska, Włodzimierz Kardasiewicz, Jan Kurkus, Mieczysław Lao, Wojciech Rowiński, Danuta Rowińska, Jadwiga Wojtulewicz-Kurkus) took place on 19th June 1969. Indeed the two decades between 1950 and 1970 saw dozens of Polish doctors visit Alwall and his clinic each year.

In June 1970 Tadeusz Orłowski invited Nils Alwall to Warsaw to give a series of lectures. The plane from Brussels with Alwall on board landed at Warsaw airport in 25th October 1970. During his stay the famous researcher gave two lectures: A Long-Term (19 years) Clinical Observation of 32 Living Patients with Acute Glomerulonephritis with Oliguria Subjected to Dialysis Treatment in 1947-1969 and Dialysis Treatment and its Problems in Sweden. All through his stay (25-28 October) Alwall was ushered in Warsaw by Zbigniew Fałda. Today, we have a pleasure to see the agenda of Alwall’s visit in the Polish capital which included dinner at the Jabłonna palace and an evening at the opera.

Zbigniew Fałda’s future professional path has led him from the Warsaw dialysis centre, which he headed, through a clinic in Seattle, USA, where he did a one-year-long apprenticeship, to the position of the Head of the Department of Nephrology and the Dialysis Centre in Bad Wildungen, Germany.

Although Nils Alwall retired in June 1971 at the age of 67 for a few following years he still held his “pensioner’s room” at the clinic. His successor as the Head of the centre was Tore Lindholm, who managed it until he retired in 1989, at which time, a Pole Jan Kurkus took over and continued until 2006.

The Polish-Swedish cooperation, which started in the 1940s, flourished throughout the next decades. It has brought the Polish dialysis treatment numerous benefits and was crowned in 1989 when J. Kurkus took Alwall’s position paying back the Polish debt to Nils Alwall and his clinic (24).

The general interest in the Clinic, especially in the development of dialysis treatment in Lund, when it was headed by Alwall’s successors was still significant, though the number of visitors was gradually decreasing. This state of affairs was largely down to the remarkable development of dialysis treatment, the appearance of new centres of nephrology and easy access to dialysis-related equipment. The Lund clinic has always been open to accept doctors and other medical personnel from Poland, both during and after Alwall’s management. Its guest book contains entries from most of the visitors including individuals who later played the main roles in the development of dialysis treatment, notably haemodialysis, in Poland, headed university clinics, departments of nephrology and regional dialysis units, toxicology and transplant centres. The list of renowned names includes: Witold Zegarski, Wojciech Witkiewicz, Teresa Wyszyńska, Kazimierz Trznadel, Zofia Wańkowicz, Andrzej Manitius, Stanisław Czekalski, Rafał Wnuk, Antoni Sydor, Olgierd Smoleński, Adam Jelonek, Ryszard Gellert, Bolesław Rutkowski, Andrzej Książek, Janusz Puka, Joanna Matuszkiewicz-Rowińska, Anna Skrzycka, Zbigniewa Śledziński, Wojciech Pruszczyński, Leszek Sadowski, Mirosław Kroczak, Marlena Ruszkiewicz, Marek Stopiński, Janusz Sadowski, Krystyna Szprynger. A very special kind of cooperation was established between the Lund centre and the Department of Nephrology and Dialysis Treatment at the Voivodship Hospital in Włocławek, Poland headed by Janusz Ostrowski. The cooperation was based on mutual week-long visits at the respective departments by doctors, nurses and technical personnel once a year in 1999-2006, the benefits of which on both sides were evident, and the list of those willing to participate in the exchange was never short.

Conclusion:

It was the primary intention of the author to highlight the considerable influence of the Swedish professor Nils Alwall and his dialysis centre on the development of Polish dialysis treatment. The great number of Polish doctors who have visited the world’s leading haemodialysis centre in Sweden in pursue of knowledge, experience and self-development must have had a positive impact on the development of the field in their home country bringing it to the present state of being on par with the best in the world.

The author wishes to thank professor Jan Kurkus for his invaluable remarks and help in preparing the paper.

 

References
  1. Cameron J.S. History of the treatment of renal failure by dialysis. Oxford University Press 2002.
  2. Ostrowski J., Rutkowski B. Początki dializoterapii w Polsce. Via Medica. Gdańsk 2011.
  3. Ostrowski J., Rutkowski B. Profesor Willem Kolff – wynalazca sztucznych narządów. Wspomnienie w 100 rocznicę urodzin. Forum Nefrologiczne. 2011; 4: 289-294.
  4. Żurowska-Kurowska M: “Sztuczna nerka” ratuje życie. Pielęgniarka Polska 1958; 10: 3-4.
  5. Hanicki Z: “Sztuczna nerka”. Możliwości zastosowania i próba wytłumaczenia działania. Doniesienie I. Przegląd Lekarski 1949; 8: 241-244.
  6. Hanicki Z: “Sztuczna nerka”. Wyniki badań pracownianych. Doniesienie II. Przegląd Lekarski. 1950; 9-10: 1-5.
  7. Hanicki Z. O zewnątrzustrojowej dializie krwi za pomocą “sztucznej nerki”. Pol. Tyg. Lek. 1957; 4: 140-145.
  8. Ostrowski J., Rutkowski B. Poczet Członków Honorowych Polskiego Towarzystwa Nefrologicznego. Cz. V. Prof. dr. hab. med. Zygmunt Hanicki. Forum Nefrologiczne. 2014; 3: 203-207.
  9. Fałda Z: Historia powstania i rozwoju Ośrodka Dializ w I Klinice Chorób Wewnętrznych Akademii Medycznej w Warszawie. Nefrol. Dial. Polska. 2009; 13: 26-51.
  10. Ostrowski J., Rutkowski B. Poczet Członków Honorowych Polskiego Towarzystwa Nefrologicznego. Cz. I. Prof. dr. hab. med. Tadeusz Orłowski. Forum Nefrologiczne. 2013; 1: 71-75.
  11. Fałda Z., Lao M. Sztuczna nerka typu Alwalla. Pol. Arch. Med. Wewn. 1960; 5: 633-637.
  12. Barg L, Leszczyński J: Życie i działalność Zdzisława Wiktora. Sprawozdania Wrocławskiego Tow. Naukowego. 1971; 26B: 6-13.
  13. Wiktor Z: Modele sztucznej nerki. Pol. Arch. Med. Wewn. 1960; 5: 626-631.
  14. Kucharz E: Prof. dr. hab. n. med. Jan Roguski- życie i działalność Członka Honorowego Towarzystwa Internistów Polskich. Pol. Arch. Med. Wewn. 1994; 94: 535-538.
  15. Roguski J: Wskazania i przeciwwskazania do hemodializy poza ustrojem za pomocą sztucznej nerki. Pol. Arch. Med. Wewn. 1960; 647-653.
  16. Ostrowski J., Czekalski S., Rutkowski B. Poczet Członków Honorowych Polskiego Towarzystwa Nefrologicznego. Część XIII. Profesor Kazimierz Bączyk. Forum Nefrologiczne. 2016; 1: 72-76.
  17. Alwall N. Leczenie sztuczną nerką 1000 przypadków w latach 1946-1958. Pol. Arch. Med. Wewn. 1960; 5: 675-690.
  18. Hornowski J. Sprawozdanie z Sympozjum “Dializa pozaustrojowa za pomocą sztucznej nerki” na XX Zjeździe Towarzystwa Internistów Polskich. Gdańsk, dn. 12. IX. 1959 r. Wiad. Lek. 1960, 2, 138-142.
  19. Alwall N., Moell H. O wielkości nerek w ostrej niewydolności nerek. Polski Tygodnik Lekarski. 1960; 43/44: 35-38.
  20. Fałda Z: W ojczyźnie sztucznej nerki. Pol. Tyg. Lek. 1960; 10: 365-366.
  21. Fałda Z: New type of arterio-venous shunt for repeated hemodialysis. Exc. Med. Internat Congr Ser. 1963; 67: 49.
  22. Fałda Z. Hemodializa za pomocą sztucznej nerki typu Alwalla. Pol. Arch. Med. Wewn. 1963; 8: 943-947
  23. Kardasiewicz W, Kurkus J, Mamont B: Wydajność sztucznej nerki typu Alwalla. Pol. Arch. Med. Wewn. 1963; 3: 269-276.
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Nils Alwall- a personal appreciation

Abstract

I first met Nils in 1964 at the founding of the EDTA (sic) in Amsterdam. I was 29, he was 60. Later I worked with him, now retired from clinical work, on committees over the next couple of decades. During this time he assumed Presidency of both the EDTA and the ISN; he was one of the major founders of Nephrology, as well as a pioneer of and major contributor to electrolyte balance, haemodialysis, ultrafiltration and related techniques. He had introduced renal biopsy in 1944, but remained silent on this subject until after Claus Brun published his work 8 years later. Nils studied arteriovenous shunts for repeated dialysis during the 1940s, but was blocked by the red rubber and glass tubing – all that was then available. I was immediately impressed by the quiet modesty of this most original man; but despite this he achieved international fame in Europe, although was never well known in the United States. His Festschrift in 1985 in Nephron amply demonstrated his status. His “rival”Pim Kolff (1911-2009) was in contrast slightly younger, outlived Nils by 20 years, and was a fine communicator and great extrovert. Nils was a physiologist and pharmacologist until 36 years old, only then becoming a clinician. Strangely Nils had performed the first haemodialysis at my alma mater, Guy’s Hospital London, in 1948 on a visit, 15 years before we established a renal unit there. Characteristically, he never told me about this event, and I only discovered the story after his death.

Keywords: Nils Alwall, History of haemodialysis, history of nephrology

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Introduction

I am grateful to Dr Håkon Westling (1, 2) for some of the following details of Nils’ early life, about which he never spoke, at least with me. Nils Andersson was born into a rather poor farming family in 1904, in an undeveloped area of Kristianstad in NE Skåne in the far SW of Sweden. His elder brother took over the family farm, but Nils – who was early on a bright scholar – matriculated and was able to go to university in nearby Lund in 1923 when only 17 years age, but only with continued financial help from an uncle, who remains a shadowy figure. Nils was a brilliant student in his undergraduate career, attaining the highest marks in almost all subjects. To begin with, he studied classics – Latin and Greek – and only later decided to read medicine during his first year in Lund, becoming an unpaid physiology research assistant in 1926. This had the advantage of providing him with somewhere to live, as well as a small laboratory and office.

Three years later in 1929 he moved from physiology to pharmacology, and graduated MD in 1932. He played an active part in student organizations, social and intellectual. He became close to the historian Lauritz Weibull and spent much time in the latter’s house. Despite his quiet exterior, Westling describes the young Alwall (he changed his name from Andersson in 1927, because “there were too many Anderssons”, but perhaps also as a break from his background and childhood) as a “pusher”, a tough customer who would fight for what he wanted (Figure 1). His politics were radical and he was concerned about the physician’s role in society. He believed strongly in education as a motor for change and better health, and gave public lectures regularly in Southern Sweden for more than 20 years.

 

Early research

In his physiological studies he worked for Professor Torsten Thunberg on intermediary metabolism. Then in 1932 he changed to pharmacology headed by Gunnar Ahlgren again on intermediary metabolism, studying dinitrophenols and thyroxine, showing that they acted similarly and synergistically. He publicly defended his PhD thesis in 1935, in the manner of the time. Sitting in the room that September afternoon was Nobel Prize-winner August Krogh, a friend of Thunberg’s whose work Nils much admired, who was to receive an honorary degree during the same session. Krogh’s work and thinking on capillary fluid exchange were an important influence on Nils’ thinking, and led him eventually into ultrafiltration and then dialysis.

In 1935-6 he spent a year in Pécs in Hungary working at pharmacology. Around this point he made a momentous decision to start clinical work. What led to this change of direction we do not know, but he started work with Sven Ingar in the Medical clinic in Lund. Meanwhile the second world war soon swept through Europe, and although Sweden remained neutral, he did military service as a doctor, being sent to Germany to study the effects of the wide use of amphetamines and other stimulants in Hitler’s forces – a subject which has re-surfaced recently*.

About this time, in 1941, he began to study fluid exchange, and to forward this work, designed an ultrafiltration apparatus for use in rabbits (Figure 2). A well-known story, which parallels Kolff’s use of material from a downed German plane to make his dialyser, is that Alwall used the new plastic Plexiglass© employed in the cockpit of an American aircraft forced to land in Sweden. He did some experiments on nephrectomised animals which could be maintained in a state of overload, and realised his ultrafilter could also remove potentially toxic solutes. Thus his work on the “artificial kidney”began – but as a secondary output from work on ultrafiltration.

He was particularly interested in accumulation of fluid in the lungs, and studied this in detail radiographically in his rabbits, some of which had been nephrectomised. He was influenced in this thinking by Krogh’s work on fluid exchange in capillaries. At first he used a flat-plate dialyser for his rabbits (Figure 2), but he was aware of the work of haematologist William Thalhimer (1884-1961) in New York, who had used cellophane sausage tubing to dialyse dogs, and managed to obtain some of this despite the restrictions of war, and built the first model of a static coil type of dialyser (Figure 3). All this was in complete ignorance that Thalhimer’s ex-collaborator, cardiac surgeon Gordon Murray (1894-1976) in Canada, would go on to build a couple of years later a similar static coil dialyser – but without any ability to control ultrafiltration. The unique feature of Alwall’s dialyser was that it had an outside glass container as well as the metal inner support for the tubing wound on it helically, which allowed the controlled ultrafiltration he sought, unlike Kolff’s rotating drum machine (of which Alwall was equally oblivious) one of whose major disadvantages was wild uncontrolled swings in the volume of body water during dialysis. Alwall pioneered the view of water as major toxin in uraemic patients. He attended the first international meeting on The kidney organized by the Renal Association of the UK in London in 1953, and described his work on in vivo ultrafiltration, and precipitated a vivid and wide-ranging discussion. In this conference dialysis was not mentioned anywhere in the programme! – and Kolff did not attend.

During the mid-1940s Alwall slowly developed his coil machine with the idea of treating renal failure in humans (3), but unlike Kolff – who never asked if he could dialyse patients, had no lab and no animal experiments – he was restrained from trying it in a human subject until June 1946, when : “…we were finally allowed to perform our first treatment in a moribund patient….As an associate professor I depended on the permission of the director of our medical department, who feared the new method. The general opinion was adverse”.

Altogether 8 patients with various types of chronic irreversible uraemia were dialysed in 1946-7 (4), but not surprisingly they achieved little long-term benefit – although temporarily they mostly felt much better for a while. However the second patient, treated in 1947 (case no 702 in ref 10, Fig 1.7 Chapter 1) had severe anuric acute glomerulonephritis, was dialyzed once – and survived. The first patient treated with dialysis for acute renal failure from mercuric chloride suicidal poisoning was fitter and also survived, but local physicians’ opinions were heavily against this form of “active”treatment, and the (to us now expected) persistent mortality of around 50-60% even in “reversible”forms of acute renal insufficiency which emerged led to a term in Sweden to describe a patient who was “Alwallized”– that is, dialysed and who then – died. Although an article in the Lancet in 1948 (5) helped greatly to disseminate knowledge of his work, the general opinion from 1945-50 was that dialysis added nothing to conservative treatment with fluid restriction and anti-catabolic nutrition (6).

This was a bleak time for him. His work, although intellectually satisfying, published and clinically useful, was however not generally accepted, he had little money despite being in his 30s, and promotion eluded him: despite having been acting professor for two years following the death of his supervisor, in 1948 he applied but failed to obtain a Professorship in medicine following Ingar’s death. Only in 1957 did he finally obtain a personal chair in Lund, in renal diseases, as his international reputation had been established. His unit in Lund, which started dialysis in June 1946, still exists and is the longest-serving dialysis unit in the world after 71 years. Ironically, not being appointed to a general medical position and finally being able to specialise saved him from the burdens of departmental responsibility, which might have allowed him no time to work and sterilized his intellect.

 

Alwall introduces needle aspiration renal biopsy

Before we consider his work in dialysis in greater detail, we must mention also his work on renal biopsy in 1944, still during WW2. By this time needle liver biopsy was well-established, and some practitioners had already obtained samples of kidney by accident. But Alwall was the first to set out deliberately to study renal tissue. He performed renal biopsies on 12 patients without incident and success in obtaining useful tissue in 10; two patients showed amyloidosis, the others – mostly with minor proteinuria or haematuria – showed tissue within normal limits judged by the technology of the day. In the unfortunate 13th patient the left kidney could not be seen on the X-ray plate but Alwall proceeded with biopsy of the right kidney obtaining inadequate tissue: the patient bled, went into shock and became anuric, despite a renal decapsulation (a technique in favour at that time) and died. Alwall published these results (7) (Figure 4) only after the Danes Claus Brun (1915-2015) and his mentor Bjarne Iversen (1889 – 1966) had written their paper on successful renal biopsy in 1951. This death must have been well-known locally, and may in part explain some of the hostility later to his promotion.

1947 was an important year as Nils made first written contact with Pim Kolff, who sent him some valuable Visking cellophane tubing, and his unit dialysed 11 patients from all over Sweden with a few from the rest of Scandinavia, on 21 occasions. Most had exacerbations of chronic disease. He talked in Copenhagen and at the Scandinavian Congress of Surgery, and in May 1948 finally met Kolff, who had been invited to meetings in Stockholm and Lund.

The arteriovenous shunt and developments in dialysis machinery

Problems with access led him to research the idea of an arteriovenous shunt, which he wrote about in 1948-9 (8). Even though these rubber and glass shunts (Figure 5) failed eventually in both rabbits and humans, a number allowed repeated dialysis (9), and it is often forgotten that by the 1950s he was able to dialyse a number of patients for 6 months or more. In 1963 (10) he wrote “these procedures – arteriovenous shunt and filling of closed tubings with heparin…- were also used in the treatments of patients … the present writer later abandoned the use of arteriovenous shunt or any other form of permanent cannulation, because of local infection and the difficulty of avoiding blood-clotting…”

For the first time Nils was able to obtain grants for his work, but even more important was collaboration with two commercial companies to build his dialyser – the Trelleborgs vulcanite company, and the Avesta steel works. He built machines using both materials (Figure 6), but by 1950 was working entirely in steel, which had the big disadvantage that the large apparatus with its double layer of metal was very heavy and difficult to lift. The detailed evolution of his machine is summarised by Carl Kjellstrand and his colleagues (12).

 

The wider world

Nevertheless there was wide interest is using his machine. Franz Volhard (1872 -1950), having survived Hitler’s Germany despite his prolonged opposition to Nazi politics, wrote asking if Alwall could loan him a machine, but at that point Alwall could not oblige. This is interesting because Volhard had opposed the use of dialysis when Georg Haas (1886-1971) used it in the 1920s in Germany (6). Alwall and Volhard met in Munich in Germany in 1949, but further collaboration with Volhard was terminated when the latter died in a car crash in 1950. But during the 1950s Nils’ machine was used in about 50 units worldwide, including first Copenhagen and Cracow (Dr Hanicki), to which he donated machines, Haifa in Israel, Newcastle in the UK, in Australia, Israel, Cuba, Australia and even the United States, where TS Danowski used it for dialysis in children in that year, and George Jernstedt of Pittsburgh collaborated to make a commercial model together with the Westinghouse company, which however did not sell in competition with newer, easier-to-use models such as the Kolff-Watschinger twin-coil disposable dialyser from Baxter Inc. Many others in central and Eastern Europe used the Alwall dialyser in the 1950s. Alwall was particularly concerned with development in of Nephrology in the then Communist bloc, and collaborated with Dutz and Klinkmann in Germany, with others in Russia, and in the (then) Czechoslovakia.

During the 1940s and 1950s Alwall collaborated mostly with surgeons who were more receptive to the idea of an artificial “kidney”than their physician colleagues. During 1947-9, 35 patients were dialysed 56 times in Lund, but elsewhere both in the USA and the UK, so-called “conservative”treatment for acute renal injury, including volume restriction and high energy diets to decrease catabolism, became more popular. This could tide patients over in relatively non-catabolic situations which included the majority of acute renal injury in that period, as a result of abortion, mismatched transfusions and haemoglobinuria, mercury poisoning and sulphonamide crystalluria in younger, previously-fit patients (6). Opinion swung against haemodialysis for a decade; in addition many surgeons and urologists used peritoneal dialysis, which had developed in parallel. For example, no haemodialysis at all was done in the United Kingdom from 1949 to 1957.

But Alwall never gave up and went on treating the rapidly increasing number of patients referred to Lund, still the only unit doing dialysis in Sweden. He worked hard to ensure that this situation did not persist, but beginning with a second unit in the North of the country in 1958, within a few years there were 17 dialysis units in the country of 7.5 million inhabitants. The struggles that he endured and overcame during the 1950s are detailed in his own account (13), and in the biography by Carl Kjellstrand and colleagues (12). By the end of the decade he had a bigger unit to head, recognition of the specialty, more staff and a personal chair – but after what a huge struggle! It took an Act of the Swedish national parliament to achieve the final steps.

By the end of the 1950s an amazing 1000 patients had been dialysed in Lund, mostly for acute renal failure, but some also knowingly or with undiscovered chronic renal insufficiency, and Alwall thought it time to summarise his experience. His book of 1963 Therapeutic and diagnostic problems in severe renal failure, (10) (Figure 7) although little known or read today, is one of the landmark publications in Nephrology. An amazing amount of data are presented, most in the form of graphs of data from individual patients, each drawn by Alwall himself and autographed. It is meticulous, but difficult to read and extract broad data from. It does however contain for the historian of dialysis an amazing bibliography of over 95% of all papers published until then on the subject of the artificial kidney – nearly 1400.

Medical advances in the field of acute renal failure and dialysis were many in the 1950s, but two require mention: in 1955 Nils described contrast-induced acute renal failure (14), and began in the early 1950s to explore the role of dialysis in the treatment of patients with overdoses of various medicines, beginning with barbiturates (15).

 

Long-term dialysis and its consequences

As is well known, in 1960 Scribner had his colleague Wayne Quinton make an arteriovenous shunt from the new electrical insulator material PTFE (Teflon©). Quinton rapidly added silicone rubber to the design, and by two important meetings later in the year (the ASAIO and the first meeting of the ISN), three patients had been using these shunts for regular dialysis for a numbers of months. In Evian at the ISN meeting, just 12 people formed the audience for Scribner’s epic paper; one of them was Nils Alwall, to whom Scribner gave some material to make a shunt.

At the end of his 1963 book (10), Alwall presented depressing data on his early attempts to use the arteriovenous shunt to treat end-stage renal failure. All 10 patients had died quite early after starting long-term dialysis. This surprise was part of an experience noted worldwide, and many wondered what “magic”Scribner and his colleagues concealed. Nils thus quietly went off to Seattle to work for some months himself there, to learn on site how to do long-term dialysis – and found that meticulous attention to detail, the use of pumpless dialysis with long sessions (6-8h) and meticulous control of weight, salt and water intake and blood pressure were the main components of the “magic”(6). He returned and re-started a now successful programme of long-term dialysis in Lund in 1964.

Only at this point when he had done so much, did I meet Nils Alwall. It was at the founding meeting of the EDTA (or ERA as it later became) – in Amsterdam, in 1964. Nils was 58, and I half his age, having worked in what became Nephrology for only three years. By chance, I have a photograph of our meeting (Figure 8), when pictures of the audience were taken during a session by Willem Drukker, one of three founders of the Association. I was in awe of this quiet, modest man who had done so much. From then, however I met him regularly through the Councils of the ISN and the EDTA-ERA during the following fifteen years, when his political achievements gradually took over from his innovation in dialysis.

 

Sweden, Europe and the world

With long-term dialysis looming as a treatment for a large number of individuals in irreversible renal failure, in all developed countries, a heated debate ensued as to what to do. Alwall played a central role in this debate not only in Sweden, but world-wide. In 1965 as he had drawn the attention of the government to the problem repeatedly, he was asked to prepare a report, which was finally accepted but only after a long struggle: 7 dialysis units in the regions of Sweden each serving a million inhabitants, were planned and executed with expansion of transplant facilities in parallel. At that time the huge size of the problem was not apparent: even Scribner pictured just a few thousands per year in the whole USA entering end-stage renal failure. And everyone forgot the patients would accumulate with successful long-term outcomes, unless transplantation could meet demand –which it still fails to do. But Alwall had done his homework better – and proposed that eventually 70 people per million per year would need treatment in Sweden, a figure close to the actual Swedish data today. Many other countries, especially the United States, showed a much greater proportion of the population requiring treatment, for reasons that remain under discussion. Had governments with central health systems realised that this 0.1% of the population with renal failure would consume more than 1% of the total health budget, their response in Sweden and the UK might have been very different. In the UK, a similar plan had been suggested by another giant of early Nephrology, Hugh de Wardener, and accepted for 35 units, but after a promising start ran aground 5 years later when costs became apparent and hepatitis ravaged the nascent hospitals.

His experience of organization and leadership in Sweden made Nils an obvious candidate for the Presidency of the ISN, on whose council he had served since it was formed in 1960, and from 1975 to 1978 he served in this high office. During this time a new constitution was designed and accepted, the finances put on a more secure footing, and a Society organization set up. He had been also President of the European Dialysis and Transplant Association in 1971 – an annual rotation with the meeting, which was held in Stockholm that year, but he served as president the following year.

 

New dialysers

Having forged his work-horse machine for dialysis in acute renal failure, Nils in the 1960s turned his attention to regular long-term dialysis. A disposable dialyzer for placement in a machine was already in use in many units for acute dialysis (the Kolff-Watschinger twin coil), and this suggested that disposable rather than re-buildable dialysers for regular long-term dialysis would be needed. After a short flirtation with coil models, he designed a flat-plate dialyser mimicking the Kiil mode, together with Holger Crafoord of Tetrapak, who founded Gambro AB as a company to manufacture this dialysis machinery. This disposable dialyser (Figure 9) came out in 1967; it was heavy with a metal clamping frame, but did the job. By 1970 it had been completely redesigned in plastic as the Gambro Lundia dialyser (Figure 9) and its successors, and were widely-used for long-term dialysis, until capillary hollow-fibre dialysers took over in the 1990s. Gambro became one of the largest manufacturers of dialysis machinery in the world.

In 1971 at the age of 65 Nils retired as university rules required, but remained active. He worked hard as President of the ISN from 1975 to 1978, and as at that time the President did much of the work of later delegated to the Secretary General, this occupied much of his attention. At that time there was no permanent office with only a couple of paid staff in the Treasurer’s office, and things were run on a very cheap basis with the President and Secretary General (John Moorhead) again doing most of the work themselves (16).

During this decade also he became interested in the problem of urinary tract infections, especially in women, and he published a number of papers on the epidemiology, diagnosis and management of this problem. In the 1980s he published a series of papers in Dialysis and Transplantation giving a detailed history of his work concentrating on events in Sweden, and later Europe and the world (13).

In 1985, the journal Nephron devoted a number to a valediction of Nils Alwall. The dedication was written by his pupil Carl Kjellstrand (14), who had worked with Nils in Lund in the early 1960s, and was a co-author of part of his giant book of 1963 (10). The same year he was invited to lecture by the International Society for Artificial Organs, and the text of this talk summarising the development and impact of the artificial kidney was published in its journal in 1986 (11) – posthumously; Nils had died, aged 81, earlier in that year. He had left behind him an enormous legacy, which Carl described more fully in his biography of Nils in the book he edited in 2012 (12).

Numbers of people have commented how Nils’ legacy has to some extent been forgotten – or never appreciated, notably Kjellstrand (12, 17), Klinkmann (18), Shaldon (19) – and the present author (6). One problem from the beginning was that Alwall remained one step behind Kolff in the design, production and use of his clinical artificial kidney (dialyzer). Also, he never promoted the treatment as vigorously as Kolff. The two were opposite poles: Kolff visibly energetic, outgoing, travelling, talking, making and giving his machines on a scale Alwall could never match. Most important of all, Kolff was invited by Isidore Snapper, also Dutch, to go to New York shortly after WW2. His talks were heard by the pioneering Boston group, and his kidney updated and modernized by them as the Kolff-Brigham dialyzer, and then employed in the battle casualties in the Korean war which gave enormous publicity and momentum to the treatment, and swung opinion against conservative treatment in traumatised and postoperative patients (6). Finally Kolff took Irvine Page’s invitation to immigrate to Cleveland, Ohio, and he never returned to Europe.

In contrast, Alwall had little or no profile in the United States, and still has not today. The great majority of his papers were published in Scandinavian journals little read in the Anglo-Saxon speaking world – or in France, where Nephrology was blossoming in Toulouse, Lyons and Paris in the 1950s. I can find no mention of any visit to the United States in the 1950s or even the 1960s, although he travelled extensively within Europe and went to Egypt in 1956. Only in 1978, because of the ISN, did he go to North America, to Montreal. Until then, no-one invited him with expenses, and he writes he lacked the means to travel to (for example) to the annual ASAIO conferences in the 1950s and 1960s. He did have visitors to Lund from the USA however – including Stefan Rosenak in 1952 (another forgotten pioneer (6)) and Scribner in 1958 whilst the latter was working in London. Scribner visited again in 1960. Finally, his disposable dialyser came a decade after Bruno Watschinger and Kolff’s massively popular twin coil, manufactured commercially by Baxter’s. As an example, in the United Kingdom only the Newcastle Unit led by David Kerr used Alwall’s machine, then quietly abandoned it for static coil dialysis. At root was Alwall’s quiet, meticulous careful and modest personality. In short, he did not “sell”himself. The steely determination remained hidden.

I will finish on a personal note. In 1948, Nils was asked by a Dr Adler to come to London to dialyse a patient in my own hospital, Guy’s Hospital. The patient had polycystic kidneys and dialysis relieved much of his symptoms. An account of this episode was published (20), but it was 14 years before we at Guy’s took up dialysis for acute renal failure. I was still at school when this early dialysis occurred and characteristically, Nils never told me about it, and I discovered the story only some years after his death in 1986, when doing research for my book on the history of dialysis (6).

 

 

*Footnote : Here I am quoting Dr Westling – Alwall himself wrote in 1980 “from the beginning of World War II until 1949 I had no opportunity to go abroad”. Perhaps he wished to conceal this episode.

 

References

  1. Westling H. Konstgjord Njure. En Bok om Nils Alwall. Stockholm, Atlantis, 2000.
  2. Westling. Personal communications, 2001-2.
  3. Alwall N. On the artificial kidney I. Apparatus for dialysis of the blood in vivo. Acta Med Scand 1947; 128: 317-325.
  4. Alwall N, Norviit L. On the artificial kidney II. The effectivity of the apparatus. Acta Med Scand 1947 (196 suppl) 250-258.
  5. Alwall N, Norviit L, Steins M. Clinical extracorporeal dialysis of blood with artificial kidney. Lancet 1948; i: 60-62.
  6. Cameron JS. The first practical haemodialysis machines: Kolff, Murray and Alwall In: A history of the treatment of renal failure by dialysis. Oxford, Oxford University Press, Chapter 8, pp 87-91.
  7. Alwall N. Aspiration biopsy of the kidney. Including i.a. a case of amyloidosis diagnosed through aspiration biopsy of the kidney in 1944 and investigated at autopsy in 1950. Acta Med Scand 1952; 143: 431-435.
  8. Alwall N, Bergsten BW, Gedda P, Norviit L, Steins AM. On the artificial kidney IV. The technique of animal experiments. Acta Med Scand 1949; 132: 392-411.
  9. Alwall N, Norviit L, Steins AM. On the artificial kidney VII. Clinical experiences of dialytic treatment of uraemia. Acta Med Scand 1949; 132: 587-601.
  10. Alwall N. Therapeutic and diagnostic problems in severe renal failure. Copenhagen, Munksgaard, 1963. p. 30.
  11. Alwall N. Historical perspective on the development of artificial kidney. Artif Organs 1986; 10: 86-99.
  1. Kjellstrand C, Lindergård B, Odar-Cederlof I. Nils Alwall, the first complete artificial kidney and the development of acute and chronic dialysis. In: Ing T, Rahman MA, Kjellstrand CM (Eds) Dialysis. History development and promise. World Scientific, New Jersey etc. 2012 pp 77-88.
  2. Alwall N. On the organization of treatment with the artificial kidney and clinical nephrology in the 1940s and flowing decades. A contribution to the history of medicine. Dialysis Transplant 1980; 9: Part I The nineteen forties: 307-311, Part II The turn of the decade 1949/1950: 475-508, Part III The nineteen fifties 559-569, Part IV The nineteen sixties the first Part 669-713, V the nineteen sixties, second part, and the nineteen seventies 752-758,771.
  3. Alwall N, Erlanson P, Tornborg A. The clinical course of renal failure occurring after intravenous urography and/or retrograde pyelography; casuistics of 11 cases (including 7 deaths) ; on indications for and risks involved in the use of contrast media, including some remarks on the risk of aspiration biopsy of the kidney. Acta Med Scand 1955; 152: 163-173.
  4. Alwall N, Lunderqvist A. On the artificial kidney XXV. Dialytic treatment of severe barbiturate poisoning in two patients. Acta Med Scand 1955; 143: 299-306.
  5. Robinson R, Richet G. International Society of Nephrology. A forty year history. Kidney Int 2001; 59: suppl 79, S-1 – S-100.
  6. Kjellstrand C. (Ed). Dedication to Nils Alwall. Nephron 1985; 39: 71-72.
  7. Klinkmann H. Historical overview of renal failure therapy – a homage to Nils Alwall. Contr Nephrol 1990; 78: 1023.
  8. Shaldon S. Alwall’s often forgotten contribution to haemodialysis. Semin Dial 2006: 260.
  9. Windschauer H. Artificial kidney at Guy’s. Guys Hosp Gaz 1948; 62: 155-157.
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