In 1962, Professor Jacques Mirouze of the Department of Medicine at Montpellier Medical School advised C.M. to join Scribner's group in Seattle. Professor Mirouze was among the very few nephrologists at that time who were convinced that Scribner's approach to the treatment of end-stage renal disease (ESRD) was right and promised to be a great development.
Upon arrival at the Division of Nephrology in the University Hospital in Seattle, it was quite clear that all the activities were concentrated on 5 East in a 50 m2 room on the fifth floor of the hospital where the three original patients received maintenance dialysis. When visiting the room for the first time, a striking feature, contrasting with the usual haemodialysis sessions for acute renal failure using twin-coil dialysers, was the absence of physician supervision once dialysis had been initiated. Dialysis technique and patient monitoring were entirely in the hands of nurses and technicians, a revolutionary approach in those days which opened the way to the extensive use of maintenance haemodialysis in the years to come. At first glance, the clinical impression was rather negative. Clyde Shields had difficulties walking with a cane and suffered from pseudo-gout; Harvey Gentry, who worked as a shoe salesman, had recurrent problems with his cannulae; Rolin Heming was bedridden due to the sequelae of a severe ascending form of uraemic neuropathy. In spite of these clinical problems, Scrib was convinced that many complications could be reversed by a more intense dialysis schedule and was certain that the survival and rehabilitation of a single ESRD patient would be sufficient to validate this new therapy. It was the time when Scrib and Bob Hegstrom, his first assistant, decided to increase the frequency and duration of dialysis sessions to three times per week for a total of 36 h: this decision was quickly followed by a remarkable improvement in Clyde Shields neuropathy and he could walk without a cane within a few months. Similarly, the prescription of oral aluminium gel as a phosphate binder resulted in a fast melting away of periarticular calcium phosphate deposits.
In June 1963, when Scrib presented these data at the 2nd meeting of the International Society of Nephrology in Prague, there was a complete turnaround of opinion and the concept of maintenance dialysis for treatment of ESRD finally was acknowledged more widely. The year 1963 was also a key time for improvements in the technology of dialysis aimed at making dialysis available to more patients by simplifying it and making it less costly. Scrib established a close cooperation with Professor Les Babb, head of the Department of Nuclear Engineering at the University of Washington. This stimulated research leading to the concept of instantaneous production of dialysate from concentrate by using proportioning pumps rather than by batch preparation. Single-pass dialysate was shown to be more efficient than recirculation, but use of a single concentrate containing all the necessary electrolytes was hampered by bicarbonate insolubility. The only available proportioning pump that could be adapted to provide the required 500 ml/min dialysate flow was fitted with two dosing chambers, but the problem persisted. A 1949 report of a study in dogs suggested to C.M. the possibility of solving the problem by substituting acetate for bicarbonate. In May 1963, C.M. proposed testing this approach in maintenance haemodialysis. Scrib agreed with enthusiasm, but he wanted an answer in 3 months! No funds were available for this unplanned research, and the Department of Biochemistry politely refused to set up the necessary acetate enzymatic dosage technique. Eager to start the study, C.M. decided to use the bedside kit developed by Scrib when he was a fellow at the Mayo Clinic and used this to measure serum and dialysate chloride and bicarbonate levels. By calculating the anion gap, he could estimate serum acetate levels and determine the acetate concentration required in the dialysate to compensate for bicarbonate losses during dialysis and to correct uraemic acidosis. By October 1963, the evidence that acetate was an acceptable alternative to bicarbonate was there! Although the use of acetate caused much controversy later on, the demonstration that it could be safely used with the Kiil dialyser was a major step in the development of the single patient dialysis machine that permitted patients to be treated at home as early as 1964. Many other events from that time would deserve mention, but particularly Jo Eschbach's early studies on the anaemia of renal disease. Also, the endless procession of distinguished nephrologists from all over the world who visited Seattle in 1963 and subsequent years was a tribute to Scrib as leader of what was then the world centre of nephrology.
When B.C. arrived in Seattle in 1972, sent over by C.M. to learn from Henry Tenckhoff about the use of his peritoneal catheter, his first encounter with Scrib was quite a surprise. Scrib said "Bernard Charra?... much too complicated... youll be Bernie!", and Bernie he has remained. At that time, the middle molecule theory was in its most active development phase. The fellows received a solid grounding in the theory from Babb and Scrib, and participated in the experimental procedures (low flow, reduced time/area, etc.) to test the hypothesis. The studies were performed at the Coach House, a former motel refurbished as an experimental dialysis unit where double blind studies were performed using volunteer patients. The place was shared with an experimental open psychiatric unit, and surprising encounters with odd characters were not exceptional!
One of Scrib's teaching topics that he and the fellows enjoyed most was fluid and electrolyte balance. He taught this course for many years. It consisted of alternating lectures and exercises on real patient cases, almost a game. This approach made the subject simple and yet very practical, and helped thousands of medical students understand the management of fluid and electrolyte problems for when they went into practice.
With so many of the renal fellows coming from overseas, the atmosphere in the Division of Nephrology was fruitfully cosmopolitan, an impression reinforced by the many visitors who made the trip to Seattle. B.C. was fortunate enough to meet Professor Jean Hamburger who, with the simplicity of a great man, told him of his pleasure in visiting Dr Scribner, especially because he remained sorry not to have recognized at the time the importance of what was going on in Seattle in the early 1960s.
In 1972, the maintenance haemodialysis unit on 5 East closed and the patients were moved from the University Hospital to the Northwest Kidney Centers headed by Chris Blagg. B.C. spent six very profitable months there seeing the operation of a large dialysis unit. During this time, Scrib asked B.C. to focus in the future on the long-term complications of dialysis as accumulated experience had shown the high prevalence of cardiovascular complications, the so-called accelerated atherosclerosis.
Back home, B.C. had the opportunity to join Dr. Guy Laurent in Tassin. Dr Laurent was using the Kiil dialyser and had maintained his patients on the empirical long dialysis schedule pioneered in Seattle. The clinical outcomes were excellent but the group was not very keen on publishing the results. Scrib did not allow this lazy issue: "Scientific data do not belong to you but to the community! You must share your experience". The advice was followed and B.C. began 25 years of close cooperation with Scrib through fax and e-mail correspondence. This gave the opportunity to discuss facts, ideas and concepts, to review papers and to exchange manuscripts. The Tassin group shared Scrib's conviction that the control of hypertension, a major index of dialysis adequacy, was best obtained by implementing a strict dry weight policy, something he tirelessly repeated from the earliest days of dialysis in 1960 to his death in 2003.
In Scrib's office, Reinhold Niebuhr's sentence, "God grant me serenity for the things I cannot change, courage to change the things I can, and wisdom to know the difference", was displayed on the wall. B.C. keeps this quotation on his desk in remembrance of Dr Scribner's lifelong dedication to the treatment of patients with ESRD.
Reminiscences of two former research fellows of the Division of Nephrology, University of Washington Medical School, 19621964; 19711973