Portal de Periódicos da CAPES

Back to the future: It does not only happen in Hollywood

2008; Elsevier BV; Volume: 73; Linguagem: Inglês

10.1038/sj.ki.5002637

1523-1755

José C. Divino Filho, Clara F. McIntyre, Johan Vestergaard Povlsen, Rebeca Puebla Paniagua,

When Dr Boen wrote his PhD thesis dissertation in Amsterdam in 1959, peritoneal dialysis (PD) was still in its initial stage of development but already saving and prolonging lives of patients with acute kidney injury (AKI) and chronic kidney disease (CKD). At that time, PD was the most frequently used dialysis option due to its simplicity and availability, and it is hard to believe that Dr Boen could envisage that, almost 50 years later, PD therapy would be a therapy of choice for thousands of patients with CKD in every corner of the world as well as an option for patients with AKI. Although the initial experiences of Professor Alwall and Professor Kolf in hemodialysis (HD) had been positive, HD development was yet limited. With the creation of the arteriovenous fistula as a permanent vascular access for chronic HD, this therapy began to evolve quickly and continuously enabling dialysis therapy for thousands and thousands of CKD patients. At that point in time, PD could not keep pace with HD, but with the advent of a permanent peritoneal access (the Tenckhoff catheter), PD started to move forward too. When Popovich and Moncrief presented the first results of continuous ambulatory PD as a new PD option, and right thereafter, Dr Oreopoulos presented the first clinical results of continuous ambulatory PD with flexible bags, PD therapy finally took off for its future; a future already foreseen and described by Dr Boen in his 1959 PhD thesis dissertation and by Dr Gjessing, a Swedish doctor, in his PhD thesis in Uppsala in 1967. The initial article in this supplement is a summary of Dr Boen's thesis, which contains a very thorough description of the PD technique, including an initial literature review from 1877 until 1958. Thereafter, Dr Boen gives attention to the kinetics of PD and the changes in plasma concentrations of several substances during dialysis (his own investigations) and then gives consideration to the management of AKI and indications for PD. In the last part of his thesis, Dr Boen concentrates on complete case histories of 22 patients treated with 32 PD treatments during the years 1951–1959, describing the results of PD and the clinical course of anuria. The second article is Dr Gjessing's 1967 thesis where he already described new osmotic agents such as amino acids (AAs) and dextran, new indications for PD such as severe hemorrhagic pancreatitis, pharmacokinetics of drugs administered intraperitoneally and as a diagnostic test in acute abdominal conditions, as well as the use of PD in the treatment of acute poisoning (more specifically barbiturates, salicylates, and methyl-alcohol). When we planned this supplement, we decided that we would like to add more depth to it by having all papers peer reviewed. At least two of the editors performed a peer review of each article, except for Dr Boen's and Dr Gjessing's, which were excerpts of their theses. It is with great satisfaction that we recognize that, although mutually very demanding, the reviews generated very interesting discussions through emails and phone calls, which certainly contributed to the quality of the articles. Gloria del Peso et al. from Spain provide a new and very tantalizing interpretation of the mechanisms associated with fast peritoneal solute transport during early PD. On the basis of peritoneal biopsies performed during the first two years on PD, their study shows that epithelial-to-mesenchymal transition of mesothelial cells is a frequent morphological change in the peritoneal membrane; they then suggest that high solute transport status is associated with its presence but not with increased number of peritoneal vessels. In the next paper, Contreras Velazquez et al. from Mexico, in another very interesting study with peritoneal membrane biopsies of 18 uremic non-diabetic, 65 uremic diabetic patients, and 15 non-uremic, non-diabetic controls demonstrate that uremia and diabetes are associated with important peritoneal histological changes before starting PD treatment. Residual renal function is of paramount importance in patients with CKD, with benefits that go beyond contributing to the achievement of adequacy targets. Marron et al. from Spain give us a very comprehensive, up-to-date, and sound review of the benefits of preserving residual renal function in PD. The innovative study by Viglino et al. from Italy, assessing the effects of an incremental dialysis protocol on the choice of dialysis modality, residual renal function, and adequacy, reports positive results. PD was chosen by a majority of the patients, and a reduction in the loss of GFR was observed in these patients when compared to the pre-dialysis period. The beauty of PD is still its simplicity, flexibility, and availability. As PD evolves, new frontiers, new options, and new indications for its clinical applications have been suggested and established. Over the past five years, PD growth in China has been remarkable and the number of PD patients has increased from 3000 to over 10 000, with an average annual net growth of nearly 30%. Chen et al. report on their study comparing the differences between two PD programs, one using the standard continuous ambulatory PD regimen and the other using an adaptative ultrafiltration (UF) approach, in order to control fluid status over time by incrementally increasing peritoneal UF along with the loss of residual renal function. Their results suggest that this strategy could effectively avoid the potential disadvantage of poor fluid control in long-term PD patients during traditional PD therapy and thereby improve patients' outcomes. An alternative option for dialysis therapy is the complementary use of PD and HD. The simultaneous use of PD and HD therapy has been studied both in established PD patients who are experiencing problems with their dialysis treatment that might otherwise prompt a change in modality, and patients new to dialysis. There are none better than Dr Kawanishi from Japan and Dr McIntyre from the United Kingdom, with their own personal experiences, to discuss the published experience of combination treatment and consider the possible benefits of such an approach. The indication of PD for the elderly patients has expanded as the proportion of elderly patients in need of dialysis is increasing steadily, but there are still barriers to be overcome. Brown from the United Kingdom makes a very clear description of these barriers, which include medical and social factors, physician bias, late referral, and education that has not been tailored to the needs of older patients. She then suggests that the development of assisted PD can overcome some of the barriers and enable frail older patients to have home-based dialysis treatment. She also refers to the fact that the option of PD for the elderly needs to be reconsidered in light of the ever increasing number of older people requiring dialysis, as placing the majority on HD will be a huge financial burden to any health-care system. An important support to Brown's conclusion is the next paper by Dr Dratwa from Belgium, where he presents the results of a European survey on the costs of home assistance for PD. The conclusion is that high reimbursement rates for assistance add significant extra cost to PD but allow granting many dependent patients all the advantages of home therapy, instead of treating them with in-center HD, which in any case still remains more expensive for our societies. With the development of the PD cyclers, a new PD modality, automated peritoneal dialysis (APD), was created that today accounts for at least 30% of the patients on PD therapy. Ramos et al. report on a one PD center experience in Mexico comparing APD to continuous ambulatory PD in a total of 237 patients, (79% diabetics) over a 3-year follow-up period. Their results show better survival and less peritonitis in the patients treated with APD; it is important to note that these results are comparable to the results published in the literature from centers in Europe, North America, Asia, and Oceania. They have a very interesting conclusion that both therapies are considered good renal replacement therapy options in their hospital, but APD is the most attractive one, as demonstrated by the positive results presented. If we go back to the initial papers in this supplement, we will read Dr Boen's and Dr Gjessing's descriptions of the use of PD for AKI and intoxications in patients of their times. In this supplement, we have a couple of studies addressing this theme in the present. Pedersen et al. present a single center cohort study based on an ICU database containing data on 1128 consecutive children undergoing their first operation for congenital heart disease between 1993 and 2002 at Aarhus University Hospital, Skejby, Denmark. A total of 130 (11.5%) children developed postoperative AKI managed with PD. The results strongly support that PD is a simple, safe, feasible, and robust dialysis modality for the management of AKI in children. Data on the use of PD for AKI in adults as well as children are reported in this supplement. Gabriel et al., in a very nicely designed and executed prospective randomized controlled trial with a total of 120 patients, compared high volume PD versus daily hemodialysis (DHD) in an University Hospital at Brazil. Metabolic control, mortality rate (58% in high volume PD and 53% in DHD), and renal function recovery (28 and 26%) were similar in both groups, whereas high volume PD was associated with a significantly shorter time to the recovery of renal function. They concluded that high volume PD and DHD can be considered as alternative forms of renal replacement therapy (RRT) in AKI. The importance of sodium and water balance in patients on PD is well shown. The results of the EAPOS study demonstrating the importance of UF in the outcome of anuric patients treated with APD are good evidence of this statement. Vega et al., in a very well-performed study, assess the impact of three predefined peritoneal UF profiles, obtained by keeping a constant glucose concentration of 1.36% (flat) or by modifying the glucose concentration of the heater bag (descendant: 38.6–1.36%; ascendant: 1.36–38.6%), on the amount of dialysis provided by APD during the nocturnal period. They conclude that the application of ascendant and descendant UF profiles in APD is clinically feasible and results not only in increased UF, thereby helping to diminish the effects of fluid overload upon cardiovascular (CV) disease and hypertension, but also in an increase in small-solute clearances, thus helping prevent inadequate dialysis. These results may have immediate clinical applicability wherever APD is used. Another strategy to improve UF in PD therapy is to use a new osmotic agent like icodextrin or a combination of osmotic agents. Dr Wilkie in the United Kingdom, Dr Freida in France, and their collaborators have been the trailblazers in this area by combining crystalloid (glucose) and colloid (icodextrin) osmotic agents in the same exchange. In this supplement, they unite their experience in one article not only making an extensive review of the literature in this area but also presenting data that had not been published earlier. Two combinations of glucose and icodextrin have thus far been evaluated for use in the long exchange, and although their characteristics differ considerably, both demonstrate efficiency of sodium and water removal and have the potential for glucose sparing when used as part of the PD prescription. The approval for clinical use of new PD solutions containing other non-glucose osmotic agents (AA, icodextrin) and more physiological buffer combinations and pH has, together with the cyclers, brought PD therapy into a new dimension, the dimension of global biocompatibility, where not only the local effects of PD solutions on peritoneal membrane are important but also the systemic effects of the same solutions play a role of utmost clinical relevance. The clinical impact of global biocompatibility by using PD solutions with optimal buffer composition and glucose-sparing PD solutions has already been observed in several studies published in the last few years, by factors such as better fluid removal control, tighter blood sugar control, attenuation of hyperlipidemia, and improved protein synthesis. In this supplement, we have studies of other salutary developments associated with the use of glucose-sparing solutions. Teta et al., from Switzerland review the leptin/adiponectin ratio, a novel marker for atherosclerosis, and elegantly evaluate its potential implications for PD, based to a great extent on their own experimental and clinical work, hypothesizing that glucose and/or other PD fluid components may affect adipokine production balance. They conclude that glucose-based PD fluids aggravate the adipokine production balance from cultured adipocytes whereas glucose-free PD fluids improve this balance, and the use of glucose-sparing PD regimen is associated with a reduction of plasma leptin/adiponectin ratio. At the end, they correctly state that whether this effect may provide novel avenues to reduce CV burden in PD patients needs to be investigated. John et al., from the United Kingdom studied in a randomized crossover trial the effects of PD fluid biocompatibility on baroreflex sensitivity comparing conventional and biocompatible PD fluids. They demonstrate that PD fluid biocompatibility modulates baroreflex sensitivity during glucose-containing PD dwell independently of glucose concentration and UF volume. This is a very unique and important study providing the first evidence of the effects of PD fluid biocompatibility on systemic CV regulation and function. Still looking into the CV impact of glucose-sparing PD solutions, in another very important and unique study, Paniagua et al. evaluated in a multicenter, open label randomized controlled trial the effects of icodextrin solutions when compared to glucose solutions on echocardiography, electrocardiography, and blood pressure changes in Mexican diabetic PD patients with high or high average transport status. Very interesting findings were observed in the early stage (6 months) and in the late stage (12 months) of the study. Their final conclusion in this randomized trial is that the use of icodextrin in diabetic PD patients is associated with better fluid management and metabolic control. Regarding the metabolic impact of the glucose-sparing PD solutions, Asola et al. from Finland compared the effects of an AA-containing PD solution to glucose-based PD solutions on skeletal muscle AA uptake in non-diabetic PD patients. The patients were studied twice in a random order and in a crossover manner both in the fasting state and during euglycemic insulin stimulation using [11C]methylaminoisobutyrate and positron emission tomography (PET). The conclusion of this scientifically elegant clinical study is that PD treatment with an AA-containing PD solution is associated with a significant increase in skeletal muscle AA uptake both in the fasting state and during insulin stimulation. All these PD solution studies have been performed in adult PD patients. There is limited experience with the use of these new solutions in a pediatric population, most reports coming from a variety of pediatric centers. However, Canepa et al. take the opportunity here to briefly review what has been published so far in this area of pediatric nephrology and, more importantly, to report their own experience with all three new generation PD solutions (AA, icodextrin, optimal buffer and physiologic pH) in their pediatric population treated with PD at the Institute Gaslini in Genoa, Italy. The value of this contribution for the pediatric community is certainly invaluable, as they show their own experience and results with different new PD solutions. Today, the utilization of glucose-sparing PD solutions is regarded as an important part of the present and the future of PD. Again, Dr Boen and Dr Gjessing already foresaw in their present the future, which is now the present for us. Moving to the end of the supplement, we now focus on large PD studies performed in countries as far as Turkey, Greece, and Canada and also in countries not far apart, situated in the same region, Latin America. Fernandez et al. report on the Brazilian Peritoneal Dialysis Multicentric Study (BRAZPD), launched in December 2004, aiming to collect data monthly and continuously from a representative cohort, allowing for a continuous snapshot of the PD reality in the country. The total number of patients recruited up to February 2007 was 3226, which represents 48% of the total number of active PD patients in the country. This initial report of BRAZPD displays the main characteristics of Brazilian PD patients in a representative cohort. The gross mortality results, comorbidity scores, and peritonitis rates observed in the Brazilian registry are not different from those reported by other international registries. The initial results of this first Brazilian PD registry provide a unique opportunity to develop future clinical studies addressing specific PD questions in the Brazilian reality and context. Yavuz et al. present a cross-sectional multicenter study carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients aimed at assessing the general status of phosphorus control and its clinical and laboratory associations in a large group of patients on PD treatment. Their results show that PD, when combined with dietary measures and phosphate binders, is associated with satisfactory serum phosphate control in the majority of patients compared with comparative HD cohorts. Moretta et al. report a multicenter cross-sectional study (Rio de La Plata study) performed in order to evaluate the prevalence of heart failure (HF) and the associated CV risk factors in 298 PD patients from Argentina and Uruguay, representing almost 30% of the total number of PD patients in the two countries. In this well-designed and conducted study, they could establish the prevalence (9.9%) of HF and identify diabetes and hypoalbuminemia as the risk factors associated with HF in their PD population. Moreover, the identification of reversible risk factors associated with HF, as well as the finding of asymptomatic ventricular dysfunction in 40% of the patients with early-stage HF will guide them to direct their efforts to establish guidelines for the prevention and treatment of congestive HF in their dialysis population. To wrap up this series of large clinical trials, Sanabria et al. report on their DOC (Dialysis Outcome in Colombia) study, which will be certainly presented and discussed in the different corners of the world. The goal of the study was to compare the survival conferred on patients on HD vs PD in a network of renal units in Colombia. The DOC study with 923 actually enrolled (47.3% of them started HD and 52.7% started PD) is a historical cohort of incident patients conducted between 1 January 2001 and 1 December 2003 with follow-up until 1 December 2005, measuring demographic, socioeconomic, and clinical variables. The final results show a trend, although not statistically significant, for a higher (12.7%) adjusted mortality risk associated with HD when compared to PD, even though the PD patients were poorer, more diabetic, and had higher comorbidity scores than the HD patients. These large studies are a message that the world of PD is still untapped and that it is feasible to perform clinical PD studies in every corner of the world. Doctors and nurses are not only thirsty for knowledge and care, but they are also ready to translate their clinical experience into studies to be shared with the PD community throughout the world. The last paper of this supplement can be considered as the last but not least evidence in this series of articles that we are back to the future. Ilabaca et al. report four cases of their extensive experience with the use of APD as a lifesaving therapy in the Emergency Room of a very busy Mexican hospital. They consider APD as a frontline acute therapy option for renal failure patients with severe hyperkalemia and metabolic acidosis in an Emergency Room. The key to their success has been a coordinated effort between Emergency and Nephrology medical and nursing staff and it is also a fact that they have received all the support from their Hospital director to implement this program. What has not been presented here is that, besides saving lives, this program has brought considerable cost savings for the Hospital. The Guest Editors would like to acknowledge the tremendous and essential contribution of Ms Rona McGreevy to the making and completion of this supplement. Her engagement from the very initial phase of planning throughout the whole process has been key to the success of this work. We would also like to thank Ed Vonesh and AR Qureshi for their statistical expertise in reviewing some of the papers here included here. This supplement is a tribute to Dr Boen, Dr Gjessing, and all doctors and nurses who developed and worked with PD in the early years of this therapy. Dr Boen and Dr Gjessing would surely never have thought that their academic accomplishments would one day be published together with articles written by doctors involved and interested in PD from the different corners of the world. Fifty years from today, someone will be reading this supplement and all these valuable contributions and will then put in perspective the last 100 years of PD. Who knows whether this person will ask her/himself the question: 'Am I living in the present or am I back to the future ?' Today, we can firmly state that we are back to the future in the untapped world of PD, and this is sound evidence that it does not only happen in Hollywood. The publication of this supplement to Kidney International was made possible by an unrestricted educational grant from Baxter Healthcare Corporation.