Originally published in Volume 36 Issue 9 of Artificial Organs, 11 September 2012
When I was a young student of the classics in high school, I was negatively impressed by the statement Ipse dixit (meaning: he, himself said it), which, by reaction, generated in me a permanent stimulus toward an accurate verification of the validity of every rule and guideline, either newly introduced or well established for a long time, with the curiosity and the need to try to surpass them and to go further. This behavior has since then guided all my life, particularly in the professional field, so that I have always considered every conquest, even the most innovative and valid (including mine) as merely temporary and possibly unprovable. And it was following this philosophy that I came to all my inventions and innovations.
INVENTIONS AND INNOVATIONS IN PERITONEAL DIALYSIS
I started in the early 1970s with the long-term treatment of end-stage renal disease (ESRD) patients with peritoneal dialysis (PD) (which at that time was almost universally confined to the treatment of patients with acute kidney failure) in order to overcome the restrictive selection criteria excluding a relatively high proportion of patients. With the aim to optimize the technique, I first switched from the largely unsatisfactory twice/weekly 40 L schedule to a daily 10 L one 1.
The next step was the substitution of the 1 or 2 L glass or rigid plastic bags with 5 L flexible plastic bags, in order to reduce the work of personnel and the high incidence of peritonitis, due to the high number of connection–disconnections and to the possibly contaminated air entering the containers to balance the depression created by the outflow of the dialysate 1, 2.
Perugia Y connection for continuous ambulatory peritoneal dialysis
Due to the very attractive and promising clinical–metabolic advantages of continuous ambulatory peritoneal dialysis (CAPD), I switched all my patients already on intermittent PD to this technique. After only a few months my enthusiasm was dramatically cooled by the peritonitis rate, which was significantly higher than during the previous treatment. It was soon clear that for the successful clinical application of CAPD on a large scale a new container-to-patient connection system was mandatory. In fact, the wearable bag system introduced by Oreopoulos was still unsatisfactory although it somewhat reduced the peritonitis rate (but not to an acceptable level) by reducing the high number of risky connection–disconnections. Furthermore, it was aesthetically undesirable to the patients. Thus, I searched for a connection system able to further significantly reduce the peritonitis rate and in the meantime to avoid the unappealing and uncomfortable need of wearing the rolled bag. I found the solution in the so-called “Y” system, which I presented for the first time in 1979 3. This system completely revolutionized the philosophy of the connection 4–10. In fact, with the wearable-bag system, the first step after the most possibly contaminating act, that is, the disconnection of the bag with the spent dialysate and the connection of the bag with the fresh solution, was the filling of the abdominal cavity. The consequence was a very high probability that bacteria would accidentally come in contact with the connection sites and would be carried down into the abdomen, where the conditions (temperature, nutrients like glucose and amino acids, long rest time) were optimal for rapid growth. On the contrary, in the “Y” system, the first step after the connection of the new bag to the catheter was a flushing of the connection with a small bolus of the fresh solution, followed by the outflow of 2 L of spent dialysate, completing the washing of the connection sites. The superior efficacy of the “Y” system was so clear that it has been universally adopted, in a modified version, by no longer mounting the “Y” on the catheter but on the bag (the double-bag system). This new procedure (flushing before filling) also enables the possible safe use of a disinfectant, because it allows for the complete removal of the disinfectant into the collecting bag. Disinfectants helped to further improve the results, especially in the less skilled and able patients (with manual and/or visual handicap), by killing any bacteria contaminating the connection sites, especially after disconnection of the bag, maintaining the sterility of the end of the catheter during the interval phases between the exchanges 11, 12.
The ideal disinfectant for PD
In order to overcome the possible side effects of the disinfectant in case of an accidental injection into the abdominal cavity, I introduced a chlorooxidant disinfectant for the disinfection of the connection system and of the catheter exit site. After careful experimentation, the disinfectant was produced with an original electrolytic method which avoids almost completely the irritative effects of sodium hydroxide, a by-product of the standard chemical production of sodium hypochlorite 13.
Automatic machine for semicontinuous PD
At about the same time, by completing and improving a previous idea 14 I researched and patented (Italian patent no. 43514 A/1979 and US patent no. 4,381,003 Apr. 26, 1983) an original automatic machine for semicontinuous peritoneal dialysis. The system was also called “accelerated equilibrium peritoneal dialysis” (AEPD) because it was able to bring to equilibrium with plasma 10 L of dialysate contained in two plastic bags, by recycling it continuously during 8–10 h nightly. In fact, thanks to the continuous stay in the peritoneal cavity of an aliquot of dialysate and to its turbulence and admixing, the extraction of solutes was comparable to that obtained with CAPD in 24 h, not only for the small but also for the middle molecules 15. The main advantages were the avoidance of the diurnal exchanges of CAPD and the halving of the quantity of dialysate needed with the standard single-pass cyclers. Another important original feature of the system was the prevention of the troublesome and possibly dangerous positive or negative peaks of the intra-abdominal pressure, thanks to a bypass at the pump level in the tube connecting the patient to the container of solution.
Physiopathology of peritoneum
My last contribution in the field of PD was the stimulating collaboration with Di Paolo and colleagues on the study of the morphology and physiopathology of the peritoneum, including the first autologous autotransplant with mesothelial cells 16–18.
INVENTIONS AND INNOVATIONS IN HEMODIALYSIS
Short daily HD
I first had the first idea of a daily hemodialysis (HD) schedule in 1975, when, at the EDTA Congress in Copenhagen, I heard the presentation by Willem Kolff on the wearable artificial kidney. Immediately, I thought that it would be more feasible, practical, and convenient to perform short daily sessions than to face the complicated and cumbersome problems of a wearable kidney. The opportunity to translate the idea into the clinical practice occurred at the beginning of 1981, when, in order to meet the request of a home HD patient to move freely from home during the holidays, I started my experience with the daily schedule. At that time, the few attempts (DePalma, Bonomini, Schneider, Twardowski, whose work I was completely unaware of) to perform a daily HD schedule for the long term had been definitively abandoned. The daily frequency was necessary, in my case, to compensate for the reduced efficiency of the portable machine (20–25 L of recycled dialysate) and for the shortened length of the sessions (limited to only 90 min in order to limit the interference with the holidays activities). In fact, due also to the relatively low blood flow (on average 280 mL/min) and to the limited area of the filters used at that time (1–1.3 m2), the resulting Kt/V was quite low: 0.35–0.50/per session, amounting to 2–3.2 or 2.7–3.7, respectively, with 6 or 7 sessions/week. The clinical and metabolic results were so impressive 19–24 that not only did the patient who first experienced the schedule ask to remain on it beyond the holidays, but also all the other patients already on a thrice-weekly home HD schedule asked to be switched to the short daily schedule (SDHD) and became themselves powerful promoters for the rapid expansion of the home HD program 25. This occurred just when home HD was declining worldwide, due to the removal of the previously sole determining motivation (i.e., the distance from the HD center) by the wide diffusion of facilities and by the growing use of the CAPD. In fact, the short daily HD with its clinical-metabolic superiority introduced a powerful and attractive new incentive and its great time flexibility due to the shortness of the sessions (now feasible during the down times of the day) removed the great interference of the longer standard schedule with the work and social life of patients and partners. The results further improved 26–33 when, in 1991, forced by the new European regulation, we adopted the standard single-pass machines and prolonged the session length up to 120 min, which allowed a better and more correct comparison vs. the standard thrice-weekly schedule (same machine and dialysate flow, same total weekly treatment time, i.e., 12 h). However, notwithstanding the growing body of positive results, it took a very long time before the scientific community could be convinced of the definite superiority of the SDHD and of its safe feasibility also on a very long term and on a large scale. This was for sure my greatest triumph, to have persevered when mine was a “voice in the desert” and I was considered the “mad Italian,” as recently reported to me by a Spanish colleague now turned an enthusiastic fan of the SDHD, like many others all over the world.
Acetate-free biofiltration (AFB)
The next step was the ideation, experimentation and introduction in the clinical practice of the AFB. The idea arose immediately when I heard the presentation of biofiltration, which was a soft hemodiafiltration combining better biocompatibility and high permeability of the polyacrylonitrile membrane, the contribution of some convective removal (3–4 L), and the advantages of bicarbonate in the reinfusate, but retaining the metabolic and cardiovascular drawbacks of the acetate still contained in the dialysate. This last characteristic of the technique was true nonsense and, consequently, I soon tried to remove the acetate from the dialysate by testing different bicarbonate concentrations in the reinfusate, until we found the right one and proved the safe and advantageous feasibility of AFB 34, 35.
Among my pioneering activities I would like to include two international meetings, which I presume have somewhat contributed to the consciousness and thus to the progress in the field of nephrology.
Meeting on dialysis schedules—Perugia 1996
This meeting, thanks to the contribution of the greatest experts in the fields of hemo- and peritoneal dialysis 36, had the merit to draw the attention of the scientific and industrial world toward the role and influence of the schedule (frequency and duration of the sessions or of the exchanges, total weekly length of treatment, blood and dialysate flow, filters surface and permeability, volume of the exchanges, the various possible combinations and interrelations between all these variants) on treatment efficiency and adequacy. In fact, after the meeting a true explosion of interest took place on this previously neglected dialytic parameter. This generated a wide debate and a great number of studies (mainly guided by many of the participants) contributing to a better knowledge of the subject and, above all, to the optimization of the dialytic treatments.
Meeting on the challenge in ESRD treatment for the near future—Perugia 1999
The aim of this symposium 37 was to bring together nephrologists, administrators, governors, and industry managers to discuss the possible ways to face the rapidly worsening problem of the cost of dialysis treatments, which, increasing steadily, could soon come to the point where it will be unsustainable without a restriction of treatment availability and a decay of quality. Many proposals and suggestions were put forth which could help to reconcile the conflicting needs of: (i) maintaining an unrestricted treatment availability; (ii) improving or at least preserving its quality and efficiency; (iii) reducing or at least keeping down the costs. The leading proposals were: (i) the early and correct nephrological treatment of patients with renal failure and their co-morbidities/complications which could significantly reduce the number of patients winding up in ESRD; (ii) an increased use of home dialysis, either PD (thanks to the reduction of its limiting complications, above all bacterial and chemical peritonitis), or HD (its revival being greatly favored by the daily schedule); (iii) diffusion of limited care centers and of in-center self care programs; (iv) introduction of the managed global care system. All the listed approaches can produce not only a containment of costs but also a reduction of hospitalization, morbidity and medications, which in turn can contribute to a further significant cost saving. After 12 years, these suggestions, whose practical application has been up to now quite scarce, are still of topical interest and their rapid implementation could be of critical importance in order to prevent a decay of technical quality and/or a shortage of treatment availability, resulting in the revival of the tragic use of patient selection.
Therefore, when I look back to draw the final balance of my professional life, I feel that I have been very lucky to have had the opportunity and the skill to add to the progress of the field of nephrology with so many, even if small, contributions.
After post-graduate studies at the School of Internal Medicine in Pisa, Dr. Umberto Buoncristiani completed his nephrology education in Pisa and Padova, and founded the Center for Nephrology-Dialysis and Transplantation at the regional Hospital of Perugia , Italy. He then went on to become a Professor of Nephrology at the Medical Faculty of the University of Perugia and at the post-graduate School of Nephrology at the same University. He contributed to the progress of many technical aspects in the field of dialysis. He is the author of more than 300 scientific papers and a member of the scientific board of many international scientific journals. Dr. Buoncristiani organized two international meetings (The Dialysis Schedule 1996 and The Challenge in ESRD Treatment for the Near Future 1999), which focused the attention of the nephrological world toward these two subjects of critical importance for the success and the future of dialysis. He is an elected member of the Council of the International Society of Peritoneal Dialysis (1990–1996) and twice of the Italian Society of Nephrology (1983–1986 and 1989–1992). He has also been honored to receive the Special Recognition Award of the Annual Conference on Peritoneal Dialysis (Baltimore 1995) and the Lifetime Achievement Award for Hemodialysis of the Dialysis Annual Conference (Tampa 2005).