PERITONEAL DIALYSIS: ADEQUACY BEYOND Kt/V

Proceedings of the ISPD '98 The VIIIth Congress of the ISPD August 23 26, 1998, Seoul, Korea Peritoneal Dialysis International, Vol19 (1999), Supplement 2

0896-8608/99 $300 + 00 Copyright @ 1999 International Society for Peritoneal Dialysis Printed in Ca nada All rights reserved

PERITONEAL DIALYSIS: ADEQUACY BEYOND Kt/V

Claudio Ronco,1 Mariano Feriani,1 Giambattista Virga,2 Gianpaolo Amici,3 and Giuseppe LaGreca1 Department of Nephrology, 1 St. Bortolo Hospital, Vicenza; Department of Nephrology,2 Provincial Hospital, Camposampiero; Department of Nephrology, 3 Regional Hospital, Treviso, Italy

for an adequate renal replacement therapy T hehassearch spurred new interest in many dialy

THE

PERITONEAL

ORGANIZATIONAL ASPECTS

DIALYSIS

PROGRAM At similar levels of clinical indication, the possibil ity of offering a free choice of renal replacement tech KEY WORDS: Adequacy; clinical parameters; homeostasis; rehabilitation; treatment integration. Correspondence to: C. Ronco, Divisione di Nefrologia e Dialisi, Ospedale San Bortolo, Via Rodolfi, 36100 Vicenza, Italy.

When organizational issues are involved, PD may represent a means for correctly allocating available resources. Peritoneal dialysis represents an important buffer that avoids further expansion of the dialysis center. In fact, while in the 1980s we were envisioning a plateau in the growth in the numbers of dialysis patients for the mid 1990s, today this forecast has been shown to be totally wrong. Hard data collected at the beginning of 1995 show that an average worldwide increase of 8.2% for HD patients and of 10.3% for PD patients continues into the period 1993-1994 (1). These figures reflect better survival on dialysis, wider criteria of acceptance, and development of some countries.

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sis techniques that potentially provide effective therapy for patients with end-stage renal disease (ESRD). In this situation, peritoneal dialysis (PD) and hemodialysis (HD) are not considered opposite options any longer, but rather represent, together with renal transplantation, various opportunities in the common field of renal replacement therapy. Peritoneal dialysis should therefore be integrated into the active treatment of uremia to offer the wid est spectrum of therapies to patients and to benefit from the organizational advantages of treating patients with different therapeutic strategies. True integration of different techniques is obtained when free selection and easy transfer of the patient from one treatment to another is made possible without restriction. Therefore, PD must be considered, together with HD and transplantation, one of the possibilities for the ESRD patient. Adequate treatment can be delivered when the most appropriate technique is selected for a patient. Furthermore, the condition of a patient at one moment in time may not be the same as it is later. Therefore adequacy must be found by continually evaluating the benefits of the current therapy and comparing them to the potential benefits of another technique. We must be prepared to transfer a patient from one technique to another, a situation only achievable when effective integration among therapies is achieved.

nique to the patient is a real obligation for the nephrologist. The patient must be correctly informed and educated throughout the period of progression of the renal disease. During periodic hospitalizations or dayhospital activities, adequate information should be coupled with accurate clinical and social evaluation. With this program of staff interventions, the patient will choose a technique with knowledge, freedom, and safety. The main message is that different techniques are interchangeable, with the possibility of free access to all of them (if clinically possible) and an easy transfer among them. Patient information and education can be adequate only when the staff (both nurses and doctors) are fully convinced that PD should be considered at the same level with other techniques. Furthermore, family collaboration, and contacts with other patients with positive experiences, should be encouraged. Once the patient has been informed of advantages and disadvantages, and family support has been assessed, the patient will be helped in making a choice by a reliable hospital team, and that choice will be accompanied by a good feeling of freedom and safety. At this point, from the ethical point ofview, all efforts will have been made to achieve an effective integration ofPD into the treatment of uremia.

defining an adequate treatment. TECHNICAL ISSUES For this reason, clinical scores or subjective analysis of the patient's well-being are important indicators of overall Peritoneal may also become technical and to treatment dialysis adequacy. Whether these aaspects areneed related mayKtN represent the unique solution in certain clinical or is urea or to treatment dose is still controversial. There logistical conditions. In this case, adequacy means to select no doubt that underdialysis is a primary cause the ofmalnutrition, more suitableacid technique. the caseimbalances, of excessive -base andIn electrolyte blooddistance from the hospital, the percentage of patients treated It pressure disorders, and central and peripheral neuropathy. withis PD may inhowever, crease from 10%antoincrease 60% ofinthe referred not clear, whether delivered dose population. When transportation problems are present, the of treatment has a linear correlation with patient survival, percentage can further increase. Increasing the dialysis dose well-being, or rehabilitation. Temporary or permanent lackresult of HD stations may render to beyond a certain point may in reduced compliance PD treatment a unique option for ESRD patients in a local area. In theand in the long run, increasing costs meantime, if a continuous bi-directional flow of patients is overwhelming the patient without significantly increasing maintained between PD and HD, the best use of the well-being and rehabilitation. available spaces will be obtained. In case of total absence of vascularTO access, CLINICAL and when ADEQUACY RELATED temporary access cannot be placed for clinical or technical reason, PD becomes essential to provide effective blood INDICATIONS purification. The situation is similar for patients with absolute intolerance to HD. this case, encounter hazards or Some patients may Inpotentially logistical problems related to extracorporeal treatments. Elderly patients, newborns, and children may

find in PD a real opportunity of treatment (3). Short term candidates to kidney transplant may be easily treated without the need to create a vascular access. Self-care and home dialysis patients might find in PD the solution for their logistical problems. Finally, patients infected with the human immunodeficiency virus (HIV) can maintain privacy and reduce exposure to dangerous contamination or to social and human discrimination. The previously claimed advantages in diabetic patients seem to be less important today, and the mortality in diabetic PD and HD patients is higher compared to non diabetic patients. However, PD requires dedicated medical and nursing staffs, dedicated spaces and rooms inside the department, and adequate evaluation of the social and clinical conditions of the candidate. Again, to identify PD as a clinical opportunity, we should emphasize the central role of the staff and its capacity to inform and educate patients. A stepby-step protocol for a patient's admittance to treatment, a description of the possible complications, and a clear statement that "PD is more than continuous ambulatory peritoneal dialysis (CAPD)" -and therefore that PD techniques other than CAPD can be used -will further increase a positive attitude in the patient. A positive attitude in the patient and a deep knowledge of the technique will prevent dropouts and treatment failure. For example, the patient must be made aware that the steady-state condition will be different from the initial phases of the therapy. On the other hand, the staff must consider that different cultural patterns will permit a different level of understanding of the disease. In this case, it is important to achieve a distinction between illusions and real, achievable targets. Good patient motivation will encourage strict adherence to dietary guidelines and drug therapy. Social and family support will permit the patient attitude to switch from dependence to sense offreedom. Finally, doctors and nurses must be aware that attempts to increase treatment dose will decrease a patient's compliance to restrictions and technical guidelines. In conclusion, patients and doctors must be aware of the potential of the therapy and the possible results achievable with the treatment. To seek for targets that the treatment cannot achieve may result in a complete failure of the treatment. THE SEARCH FOR HOMEOSTASIS AND REHABILITATION How can adequate homeostasis be obtained? Peritoneal dialysis may deliver adequate results when the hydration condition of a patient is close to normal. Because CAPD should lead to steady-state body weight, an accurate balance must be achieved between


fluid intake and removal. case, the preservation of With such growth, In HDthis centers would become insufresidual renal function may become a critical factor to help ficient to provide adequate therapy to all patients in the fluidabsence balance. Sodium balance canPDbeas monitored and of the possibility of using a parallel therapy. adequately managed by influencing peritoneal ultrafiltration Using PD, the number ofHD stations can be maintained andunchanged, oral intakes. a consequence of these two can aspects, andAsmedical and nursing staffs remain blood-pressure control can be maintained with better resultsand adequate. Peritoneal dialysis also permits the program compared corporeal HD where fluidhas shiftsbeen and blood conceptto extra of home dialysis, which partially volume changes are more common and, in some cases, abandoned for HD, to be kept alive. inevitable. Inadequate control of acid-base and other elecAdditionally, while in the past PD represented a limitrolyte disorders may result from inappropriate treatment tation to a patient's candidacy for kidney transplant, today schedules or from malnutrition, andlist dietary PD patients are well accepted incatabolism, any transplant without disorders. In allThe of these cases ,isthe limitations dialyzed, imposed by restrictions. PD patient continuously being PD the should always be borne in mind. A shift to another ideal candidate in a waiting list. Furthermore, a late technique signs of shown clini caltoinadequacy removalmay of be thesuggested catheter ifhas been be safe and are without clearly demonstrated, whether Kt/V specific complications (2). values are adequate or inadequate. TheCLINICAL final targetPARAMETERS of renal replacement therapy is to obtain OF ADEQUACY the full social and physical rehabilitation of the patient. With this in view, PD cancomes offer specific advantages The goal term adequacy from Latin, where leading to a good chance for effective rehabilitation. "adequatum" means "equal to". With all our efforts, we are The patient's social and working life that may equals benefitthe from still very far from providing a therapy native an effective integration of PD into the renal re placement renal function. We should bear in mind that human kidneys therapy program. is and a out-of-hospital treatment, are not a simplePD filter, that purifying the blood of not waste needing a machine in most cases, and using procedures products is not the kidneys' sole function. Thethat final reduce stressofatkidney the minimum. self-care treatment in meaning function Itis isthea constancy of the internal which the patient the chanceoftohomeostasis. plan holidays and travel. milieu and the has maintenance Based From on these features, and on continuous staff support, this perspective, the maintenance of fluidtheand patient experiences a unique sense of safety and freedom. electrolyte balance is one of the most important targets of Thisthefeeling is further accompanied by the certainty that,and treatment. Blood-pressure control, acidbase control, when possible or needed, HD will always be available and a the correction offactors involved in uremic toxicity, anemia, kidney transplant is not precluded. and damage to various organs are other important aspects

TECHNICAL ISSUES Peritoneal dialysis may also become a technical need and may represent the unique solution in certain clinical or logistical conditions. In this case, adequacy means to select the more suitable technique. In the case of excessive distance from the hospital, the percentage of patients treated with PD may in crease from 10% to 60% of the referred population. When transportation problems are present, the percentage can further increase. Temporary or permanent lack of HD stations may render PD a unique option for ESRD patients in a local area. In the meantime, if a continuous bi-directional flow of patients is maintained between PD and HD, the best use of the available spaces will be obtained. In case of total absence of vascular access, and when temporary access cannot be placed for clinical or technical reason, PD becomes essential to provide effective blood purification. The situation is similar for patients with absolute intolerance to HD. In this case,

the transfer to PD can be temporary or permanent, depending on the evolution of the clinical pattern. PERITONEAL DIALYSIS IS A FULL TREATMENT FOR ESRD A full conviction that PD represents a real therapeutic option for ESRD patients is necessary to achieve a real integration of this therapy into the uremia treatment program. A positive cost-benefit ratio, both from the clinical and the economic points of view must also be sought. The patient must receive the same positive conviction indirectly, based on solid data and clinical results comparable to those achievable in HD. Furthermore, the patient must know that such treatment will provide an equal opportunity for kidney transplant compared to other therapies. Positive feelings must also be encouraged by information on patient survival, rate of complications, treatment adequacy, availability of different techniques within the treatment, and complete summary of advantages and disadvantages. From recent data in the literature (4), PD and HD do not seem to differ in respect of morbidity and mortality rates. CAPD patients have a greater need for hospitalization, mainly owing to peritonitis, while HD patients have a greater incidence ofintradialytic and peridialytic cardiovascular instability, arrhythmias, and extracellular fluid volume expansion. Diabetes negatively affects survival both in CAPD and in HD; no significant differences in the evolution of diabetes have come out. Method survival is worse in CAPD, but patient selection criteria exercises a strong influence and a definite "center effect" is seen. All things considered, patient survival does not differ for the two methods; but, for older patients, survival seems to be better in CAPD. Incidence of peritonitis affects the risk of death in PD patients. This is an important complication that has, however, been dramatically reduced in the last five years. The advent of the Y-set and the adjusted analysis of peritonitis incidence has shown an average rate of 1 episode per 30 patient-months. This incidence is the average of two populations: peritonitis free patients and frequent relapsers. If a correct clinical evaluation of the causes inducing frequent relapses of peritonitis is done, the incidence of this complication can probably be further reduced. The 1990s have been a period in which, after peritoneal transport was studied and a reduction in the peritonitis rate achieved, adequacy of treatment has become a main issue to define the therapy as completelyreliable. Recent studies (5) have demonstrated that despite a lower Kt/V compared to HD, CAPD can provide adequate treatment. In particular, early studies showed


fluid intake and removal. In this case, the preservation of residual renal function may become a critical factor to help fluid balance. Sodium balance can be monitored and adequately managed by influencing peritoneal ultrafiltration and oral intakes. As a consequence of these two aspects, blood-pressure control can be maintained with better results compared to extra corporeal HD where fluid shifts and blood volume changes are more common and, in some cases, inevitable. Inadequate control of acid-base and other electrolyte disorders may result from inappropriate treatment schedules or from malnutrition, catabolism, and dietary disorders. In all of these cases, the limitations imposed by PD should always be borne in mind. A shift to another technique may be suggested if signs of clini cal inadequacy are clearly demonstrated, whether Kt/V values are adequate or inadequate. The final target of renal replacement therapy is to obtain the full social and physical rehabilitation of the patient. With this goal in view, PD can offer specific advantages leading to a good chance for effective rehabilitation. The patient's social and working life may benefit from an effective integration of PD into the renal re placement therapy program. PD is a out-of-hospital treatment, not needing a machine in most cases, and using procedures that reduce stress at the minimum. It is a self-care treatment in which the patient has the chance to plan holidays and travel. Based on these features, and on continuous staff support, the patient experiences a unique sense of safety and freedom. This feeling is further accompanied by the certainty that, when possible or needed, HD will always be available and a kidney transplant is not precluded.

very steep and clearance shows significant changes even in the presence of minimal changes in the dialysate flow. We should remember, however, that minimal variations in the dialysate flow such as 1.2 mL/min may require a move to 4 exchanges or 5 exchanges per day. This region is therefore dialy sate-flow-dependent or flow-limited, because the volume of the dialysate per day is the factor that most limits the clearance value. In this region, it would be theoretically simple to increase dialysate flow by a few milliliters per day to achieve much higher clearances and, consequently, significant increases in Kt/V. However, while theoretically possible, such a change would become, in practice, unfeasible, as it would mean carrying out between 6 exchanges and 10 exchanges per day. While such a regime can be carried out for a critically ill patient admitted to the hospital, it is absolutely impossible for patients on an ambulatory regimen. In fact, for an acceptable rehabilitation, the patient should not spend vast amounts of time performing dialytic exchanges. In conclusion, typical CAPD technique is basically dialysate-flow-limited. When an attempt is made to overcome flow limitations, social and patient-related limitations take over, and efficiency cannot be increased. The only possible way to increase dialysate flow without increasing the number of the exchanges is to increase the volume of solution per exchange. This approach has been underestimated in past years, and we must probably take it into consideration as a standard for the coming years. To achieve the same fractional clearance in patients weighing 60 kg and 90 kg, one must schedule 4 exchanges per day with 2 L and 3 L bags respectively. The impact of possible rises in intraperitoneal pressure must be carefully checked to avoid middle-term to long-term complications such as hernias, respiratory problems, or decreased ultrafiltration. With an increase in the dialysate flow rate, the relationship of flow rate with clearance enters the typical region of APD. The dialysate flows may vary significantly owing to a variation in the dwell time from 30 minutes to 0 minutes, and in the number of exchanges per day. Assuming a 30-minute dwell time and 20 minutes for inflow and outflow, 12 2-L exchanges can be performed overnight, for an overall duration of 10 hours. The clearance will be 19 mL/ min or 11.4 L/day. When the dwell t ime is reduced to 0 minutes and the dialysate flow is therefore in creased, the clearance rises above 30 mL/min with a total clearance per day of 18 L. This would correspond to a rise in the weekly Kt/V from 2.21 to 3.50 in a 60-kg patient. This treatment, which could be defined as high-flow APD, would however require 60 L of dialysis solution. Such a quantity is much higher than what today's cyclers can handle, and the cost for such


that a weekly KtN of 1.7 could be enough to provide adequate treatment in CAPD patients. Analyzing a fully rehabilitated population, we could confirm that weekly Kt/V was in the range of 1.77 for urea (6). In the same study, we could achieve an exponential correlation between weekly Kt/V and protein catabolic rate, suggesting that when a certain level of therapy is provided, protein intake reaches a plateau, becoming dependent only on the free choice of the patient. A simple calculation can therefore be performed in CAPD to assess the number of liters of dialysis solution required in a totally anuric patient to achieve the desired weekly Kt/V, assuming a complete dialy sate/plasma equilibration. Recent preliminary reports from the CANUSA study (Nolph KD. Oral presentation at the Italian Society of Nephrology Meeting, Genova, 1995. Personal communication) have suggested, however, that a higher level of efficiency should be pursued and that Kt/Vvalues between 1.9 and 2.1 should definitely be obtained to increase the patient's survival. As suggested by Cancarini et al (Cancarini G. Oral presentation at the Italian Society of Nephrology Meeting, Genova, 1995. Personal communication), a careful analysis of the prescribed dose should be carried out in such conditions, mostly when higher efficiency levels are chosen as a target. In fact, it is evident that as long as the target KtN is increased, and the patient's body weight increases, exchange volumes and the number of daily bags should be increased as well. We must be careful, however, as high volumes are claimed to increase complications and discomfort, while an increased number of exchanges per day may dramatically reduce compliance by the patient and the patient's feeling of freedom, with possible treatment failure and poor rehabilitation. In conclusion, we may speculate that we should probably avoid seeking a treatment whose results and objectives can be only seldom achieved. These difficult attempts may, in some cases, yield such negative effects as to cause a complete failure of the therapy. The availability of different PD techniques is today a reality. Continuous cycling peritoneal dialysis (CCPD), different forms of automated peritoneal dialysis (APD), nightly treatments, and so on must be available in the dialysis center. For effective utiliza tion, dedicated rooms and stafffor training and teaching are definitely required. On the other hand, an accurate evaluation of the patient and of the patient's peritoneal membrane characteristics is fundamental to providing the basis for the correct indication of technique. When urea clearance is plotted against the dialysate flow rate, the relationship presents three specific regions. The first region includes the dialysate flow rates typical for CAPD (3 exchanges to 5 exchanges per day). In this region, the correlation is

lation. In this approach, the analysis of the cost of uremia treatment per million population will include preventive measures, replacement therapies, the transplant program, related drug therapy, and hospitalization. TOWARDS THE FUTURE In the recent European Dialysis Transplant Association (EDTA) conference in Geneva (September 2024, 1997), an international survey disclosed the results obtained in more than 2000 forms submitted to nephrologists and nurses in Europe and in N orth America. The main question related to PD asked which change should be the most important to attain for better composition of the PD fluid and long-term peritoneal membrane preservation. Considering the problems related to ultrafiltration loss, direct membrane damage caused by glucose and indirect damage caused by glucosederived products, the problems of bioincompatibility generated by lactate, and the inflammatory action of an acidic solution, more than 50% of the answers suggested the substitution of an alternative osmotic agent for glucose. More than 25% of the answers suggested using a bicarbonate solution instead of lactate, and 20% proposed using a solution with a neutral pH. The ongoing studies on PD are indeed oriented towards these objectives, and the first results are close, mostly as far as bicarbonate PD solution is concerned. In the long term, the peritoneal membrane will probably benefit from the new technical and biochemical approaches. The substitution of other osmotic agents for glucose appears less easy, although some recent studies with icodextrins, glycerol, and amino acids seem to be promising. REFERENCES 1. Baxter Healthcare Corporation. Worldwide survey on renal replacement therapies [Annual report]. 1995. 2. Chiaramonte S, Bragantini L, Scalco G, Feriani M, Conz P, Ronco C, et al. Late removal of the peritoneal catheter in transplanted CAPD patients. In: Ota K, ed. Current Concepts in Peritoneal Dialysis. Proceedings of the Fifth Congress of the International Society for Peritoneal Dialysis, July 21-24, 1990; Kyoto, Japan. Amsterdam: Excerpta Medica; 1992:753-6. 3. McDonald M, McPhee PD, Walker RJ. Successful selfcare home dialysis in the elderly: A single center experience. Perit Dial Int. 1995; 15:33-6. 4. Maiorca R, Cancarini G. Outcome of peritoneal dialysis: Comparative studies. In: Nolph KD, Gokal R, eds. Textbook of Peritoneal Dialysis. Dordrecht: Kluwer Academic Publishers; 1994:699-734. 5. Keshaviah PR, Nolph KD, van Stone JC. The peak urea concentration hypothesis: A urea kinetic approach to


treatment may become excessive. A good compromise could be the use of a tidal volume of solution that may contribute to artificially increasing the dialysate volume and to a better utilization of the surface area available for the exchanges. Further increases in dialysate flow rate demonstrate a plateau in the relationship between urea clearance and flow rate. In this region, further in creases in dialysate flow rate do not result in parallel increases in clearance. This region has been experi mentally explored using high-speed cyclers and largebore intraperitoneal catheters (6). The plateau has been also studied with computerized models based on calculation of the mass transfer area coefficient (MTC). The value of the mass transfer coefficient is a function of the overall permeability of the peritoneum multiplied by the available surface area of the membrane. This parameter is based on a calculation, made for each individual subject, of the maximal clearance theoretically achievable at infinite blood and dialysate flow rates -that is, at the constantly maximal gradient for diffusion. Kinetically speaking, the clearance value tends to decrease over time within the duration of one exchange, owing to a progressive dialysate/plasma equilibration with a parallel reduction of the gradient for diffusion. The MTC is then mathematically calculated as the intersection of the clearance curve with the y axis at the zero time of one exchange, where the gradient for diffusion is maximal. In rapid PD exchanges and intermittent dialysis techniques, the limitations imposed by the peritoneal MTC should be carefully considered. Whether these limitations are imposed by the permeability of the membrane or by the blood flow rate in the peritoneal capillary network as suggested by the "nearest capillary hypothesis" (7) is not clarified yet. It should be remembered, however, that clearance limitations are specifically linked to different dialysis techniques and optimization of the therapy means identifying the more suitable therapy for each patient. Residual renal function, the patient's dietary intake, and effective treatment efficiency should be periodically controlled for this purpose. When a transfer to HD, temporary or permanent, becomes mandatory (for whatever reason), doctors, nurses, and patients should understand that the transfer is a natural event when a real integration among treatments is operational. Finally, to achieve a complete integration of PD in the treatment of uremia, a detailed analysis of costs should be undertaken. However, while differences can be found in the costs of single techniques, the correct approach to the problem should probably imply an overall evaluation of the costs of the entire renal re placement therapy program in a given area or popu

comparing the adequacy of continuous ambulatory peritoneal dialysis ( CAPD ) and hemodialysis. Perit Dial Int. 1989; 9:257-60. 6. Ronco C, Bosch JP, Lew SQ, Feriani M, Chiaramonte S, Conz P, et al: Adequacy of continuous ambulatory peri

toneal dialysis: Comparison with other dialysis techniques. Kidney Int. 1994; 46(Suppl 48):SI8-24. 7. Ronco C. The nearest capillary hypothesis: A novel approach to peritoneal transport physiology. Perit Dial Int. 1996; 16:121-5.
