Proceedings of the ISPD '98 -The VIIIth Congress of the ISPD August 23 -26. 1998, Seoul. Korea Peritoneal Dialysis International, Vol. 19 (1999), Supplement 2 0896-8608/99 $300 + 00 Copyright © 1999 International Society for Peritoneal Dialysis Printe d in Canada AIl rights reserved AUTOMATED PERITONEAL DIALYSIS: WHEN AND HOW TO DO IT Gianpaolo Amici,1 Giovambattista Virga,2 and Claudio Ronco3 Nephrology Division, 1 S. Maria dei Bat tu ti Hospital, Treviso; Nephrology Service,2 P. Cosma Hospital, Camposampiero; Nephrology Department,3 S. Bortolo Hospital, Vicenza, Italy peritoneal dialysis (APD) is A utomated growing dialysis treatment in the world at the fastest KEYWORDS: Automated peritoneal dialysis; treatment prescription; treatment monitoring; solute removal index; patient selection. Correspondence to: C. Ronco, Department of Nephrology, S. Bortolo Hospital, Viale Rodolfi, 36100 Vicenza, Italy. SHORT GLOSSARY OF APD TECHNIQUES The nomenclature of various APD schedules has been widened in recent years owing to slight modifications of the different techniques. It is therefore important to define the various schedules using a common terminology that permits standard definitions in the international literature. The following terms are today in use: .Automated peritoneal dialysis (APD): This broad term encompasses every type of peritoneal dialysis performed with the aid of a machine, also called a cycler, regardless ofmodality: nightly only or continuous, tidal or not tidal (1,7). .Nightly intermittent peritoneal dialysis (NIPD): NIPD is APD performed nightly only, with complete fill and drain of the peritoneal cavity (intermittent flow technique or non tidal modality) (1,7). .Nightly tidal peritoneal dialysis (NTPD): NTPD is APD performed nightly only, with partial fill and drain of the peritoneal cavity (tidal modality, also called "reciprocating" in the past) (1,7). .Continuous cyclic peritoneal dialysis (CCPD): CCPD is APD performed nightly (intermittent flow technique or non tidal modality), with the addition Downloaded from http://www.pdiconnect.com/ by guest on September 16, 2014 the present time. The evolution of this peritoneal dialysis (PD) modality is closely linked to the development ofnew automatic machines and to recent advances in prescription and monitoring of PD treatment. Since 1960, machines have been introduced to perform semiautomatic or fully automatic PD treatment. In the early days, peritoneal dialysis was mostly intermittent (IPD), featuring a total of 24 hours per week divided into three or more sessions. The applied technology was similar to the hemodialysis machines of those years. The slow peritoneal transport of solutes limited the efficiency of the treatments (1). In recent years, knowledge derived from the equilibration dialysis concept of continuous ambulatory peritoneal dialysis (CAPD) and the availability of plastic bags (2) have contributed to a rediscovery of intermittent peritoneal dialysis techniques. APD has today become a daily home treatment with automated nightly exchanges and one or two daily dwells, following the concept of reversed CAPD (continuous cyclic PD: CCPD) (3,4). The development of ad hoc machines, easy to use and with a simpler operator interface (the cyclers) (1), represented a further key factor in this process of evolution. Another important step in APD is represented by microchips and computers. These components, incorporated into PD cyclers, gave the machines greater programming flexibility. Thanks to these innovations, it is now possible to prescribe individualized fill volumes, variable tidal volumes and additional daytime automated exchanges, teledialysis, and memorized delivery control. At the same time, miniaturization of all components now allows full portability, owing both to reduced dimensions and to light weight (5). Today in the U.S.A.,APD is used by 31.9% ofall PD patients, including daytime dwell mode, daytime empty mode, and schedules with one or more additional manual exchanges (6). Because CAPD has recently displayed its limitations and new trends are aiming at increasing the dialysis dose in peritoneal dialysis, newer PD techniques alternative to CAPD seem to represent the answer to the new requirements. Higher adequacy targets, together with the search for a better quality of life, seem to be more easily matched by APD. The possibility of using newer dialysis solutions represents a further step in the increased application of automated peritoneal dialysis techniques. of one (CCPD1) or two (CCPD2) daytime dwells (1,7). .Continuous tidal peritoneal dialysis (CTPD): CTPD isAPD performed nightly (tidal modality), with the addition of one (CTPD1) or two (CTPD2) daytime dwells (1,7). .Intermittent peritoneal dialysis (IPD): IPD is APD treatment prescribed mainly for a total duration of 24 hours per week divided into three or more sessions. The dialysate flow is continuous: that is, without dwells (1,7). .Borderline techniques: These techniques involve CAPD with one or more automated exchanges using simple machines without all the characteristics of a modern cycler. These techniques reduce the number of connections and can aid patients performing additional exchanges (8,9). PRESCRIPTION AND DELIVERY OF Optimal fill volume (individualized for body size and intraperitoneal pressure) (10,11), individual peritoneal transport characteristics (12,13), and total prescribed dialysate volume per session are the most important parameters influencing efficiency and limiting APD adequacy. Using NTPD only, patients with a 4-hour creatinine (Cr) D/P > 0.65 and total volumes between 25 L and 30 L per session can reach a peritoneal creatinine clearance (CrCl) higher than 50 L per week (14). This result is also confirmed by Twardowski et al who found an average CrCl of 47 L per week in NTPD patients with a mean Cr D/P = 0.66 (15). Using CTPD2 (two diurnal dwells) in anuric patients, only those with a Cr D/P > 0.65 can reach both Dialysis Outcomes Quality Initiative (DOQI) targets (Kt/V = 2.1 and CrCl/ 1.73 = 63 L/week), but total dialysis volumes of more than 20 L/1.73 per session are needed (16). Using NIPD with a mean 14 L total volume per session, a mean CrCl/1.73 of27 L/week was obtained in 7 patients (74 kg, 1.8 m2) with a mean Cr D/P = 0.68 (17). Another study demonstrated a CrCl of 42.5 L per week and a Kt/V of 1.55 in 9 patients (75 kg mean body weight) on NIPD with a total volume per session of about 10 L (18). Both studies demonstrated that, despite a good compromise between efficiency and number of liters prescribed having been sought, when volumes lower than 20 L per session in NIPD are used, inadequate results are likely to be expected. Thus, for all APD techniques, only patients with a peritoneal permeability higher than the mean (high and highaverage) can reach adequacy targets with a total volume per session not less than 20 L/1.73. Tidal modality, usually prescribed at 50% exchange volume, has demonstrated equal or superior clearances to non tidal modalities using the same dialysis TREATMENT MONITORING The prescribed dose does not always correspond to the delivered dose. Catheter malfunction, changes in peritoneal transport, and poor patient compliance are the main causes. Catheter malfunction can be detected by periodically measuring inflow and outflow times. Changes in peritoneal transport can be suspected when blood chemistry changes in the presence of a constant PD regimen. A peritoneal equilibration test (PET) should therefore be prescribed and compared to previous results. To effectively monitor cycler function and patient compliance, two possibilities exist: the "electronic" method, based on machine control, or the "human" method, with frequent home visits. Removable memory storage is now available to register all data from home sessions, and telecommu nication systems can connect the center and the cycler Downloaded from http://www.pdiconnect.com/ by guest on September 16, 2014 APD time and volume (19,20). The major advantage of this method is the increase in dialysate flow with shorter exchange times and, consequently, the possibility of raising total prescribed volumes (14,19,21,22). A rational approach to increase peritoneal clearance in APD must consider using tailored fill volumes. Because intra-abdominal pressures are higher in the sitting position than in the upright and supine positions (23), larger volumes of dialysate are better tolerated while the patient is supine, as during nocturnal APD. Increased and individualized dwell volumes, and prescriptions for suitable total volumes per session in APD, permit longer dwell times and allow for better results in patients with a peritoneal permeability lower than the mean. Common dwell volumes in APD are 40 mL/kg (21) or 2.5 L/1.73 (9,10). It has been suggested that intra-abdominal pressure values be kept below 18 cm H2O (11). Increased intraabdominal volume and pressure can lead to reduced ultrafiltration and, consequently, can reduce the expected clearance increase in APD (24). Another approach to reach an optimal APD pre scription in every single patient is to consider computer-assisted kinetic modeling (25). Programs for this purpose are easily available -PD Adequest (Baxter Healthcare, Deerfield Illinois, U.S.A.), Pack PD (Fresenius Medical Care, Bad Homburg, Germany), PDC (Gambro AB, Lund, Sweden) and all have in common a reliable mathematical model describing the peritoneal dialysis system and an individual peritoneal function test as data entry (26-33). With all of these programs, it is possible to simulate APD regimen results to iteratively achieve the desired optimi zation in each patient. solutes is markedly different in intermittent and continuous treatments (34,37-39). Mter the "peak concentration hypothesis," the proposal of solute removal index (SRI) as an adequacy index that overcomes all the compartmental problems seems interesting. The rationale for SRI is that the removed solute mass is normalized for the pre-dialy sis compartment (body) content. Pre-dialysis urea and creatinine compartments are effectively best equilibrated because they are as distant as possible from the end of the previous treatment (37-40). In that moment (pre-dialysis), blood is fully representative of total body water concentration. Because SRI considers solute body content, it is actually easy to calculate only for urea and creatinine that are distributed in total body water. SRI has for urea the same value and significance as Kt/V, while for creatinine it represents the Kt/V of that solute. This last index is very seldom used but has the same rationale as urea Kt/V because creatinine has the same distribution compartment (total body water) (41). It now appears clear that SRI is different from the classical Kt/V and CrCl only in using pre-dialysis blood concentration. Thus, by using the pre-dialysis blood concentration for standard (direct measurement) ofKt/V and CrCl, all the compartmental problems are easily avoided, eliminating the need for increased or different adequacy targets in hemo dialysis, CAPD, NIPD/NTPD, or CCPD/CTPD (40,42). Using a double index (Kt/V, CrCl), target discrepancies can present a problem: that is, one clearance above the target value and the other clearance below the target value. Target discrepancies have been reported in several papers, in both APD (16,42) and CAPD ( 43,44). The most common finding is that Kt/V easily reaches adequacy targets while CrCl does not. Factors affecting this discordance are the intermit tent nature of APD treatment (42), the degree of residual renal function (43), and the peritoneal transport characteristics (15,44). It is recommended in cases of discordance between the two indices that Kt/V should be given primacy (36,45). Previous studies have already reported that a considerable day-to-day variability exists in adequacy indices derived from 24-hour collections in PD. This variability affects the evaluation of dialysis adequacy in any PD modality. Consequently, when single measurements are close to adequacy targets, it is advisable to repeat them to reduce the variability (46,47). The CANUSA study represents a big effort towards determining optimal indices and targets in CAPD (48). However, that study was conducted without randomization into different dose groups, and, consequently, it has not answered all questions about PD adequacy. Moreover, no APD patients were studied; the question if APD can give better outcomes than CAPD is Downloaded from http://www.pdiconnect.com/ by guest on September 16, 2014 at the patient's home. The first system seems more practical; but, with the expansion of teletransfer of data via cable or satellite, the future spread of teledialysis is to be expected. However, the direct measurement of clearances is crucial in the assessment of treatment adequacy. Creatinine and urea clearance are the most widely used adequacy indexes in peritoneal dialysis and thus in APD. Commonly, creatinine clearance is normalized to body surface area and urea clearance to body water (Kt/V) and expressed on a weekly basis. In a steady-state condition, the calculation of clearance (that is, the ratio between dialysis removal and body concentration) entails the direct measurement of removal by total fluid collection and assay, and a plasma sample that represents the body compartment concentration of the considered solute (34). In APD, with a high-efficiency nightly treatment and dry days or 1 -2 diurnal dwells, the intermittence or the variable intensity of the therapy causes a compartmental disequilibrium effect that is expressed by fluctuations in plasma concentrations between the predialytic (evening) and post-dialytic (morning) plasma values (16,18). This difference is more marked for urea than for creatinine (18). The use of the post-dialytic plasma value in clearance measurement, which is lower than the pre-dialytic value, significantly overestimates Kt/V by 6.3% (18) to 14% (16). The variability ofoverestimation is due to the different efficiency of APD and consequently to the different compartmental effect. It is actually considered standard practice that the blood sample be taken during the day at a time equally distant from the previous and the subsequent nocturnal APD sessions (35). This practice is equivalent to calculating an averaged mean of blood concentrations; but, is the composition of all body compartments well estimated using this method? Following the concept of intermittence or variable intensity, it is common opinion that optimal adequacy targets are higher in NIPD (Kt/V = 2.2 and CrCl/ 1.73 = 66 L) than in CCPD (Kt/V = 2.1 and CrCl/1.73 = 63 L), and that both are higher than those in CAPD (Kt/V = 2.0 and CrCl/1.73 = 60 L) (36). The problem of different adequacy targets with different treatments is again dependent on the effect of blood concentrations on the calculation of clearances. The difference in targets between hemo dialy sis and PD has the same origin (34). Treatments that differ for intermittence and intensity present extremely different blood profiles. These blood profiles are not representative of total body composition, and in various moments they present a non linear dynamic compartmental disequi librium. Moreover, pre -dialysis blood concentration of open. For trial design purposes, the use of indices not influenced by compartmental effects can allow an easy and direct adequacy comparison between different APD and CAPD techniques. PATIENT SELECTION CRITERIA FOR APD NEW CLINICAL ASPECTS AND FUTURE TRENDS OFAPD In APD, the use of new solutions with alternative osmotic agents, nutritional integration, reduced sodium content, and alternative buffers seems very promising (51,52). As soon as bags and connections for APD are available, it will be possible to use mixtures of various solutions tailored to patient needs. In APD, amino acids together with glucose are very promising because of the simultaneous absorption of calories and nitrogen for protein anabolism. The optimal proportion of glucose to amino acids in the mixture can be 7:1, giv ing an approximate intake of 1 g of nitrogen for every 112 kcal. This mixture has been used in a long-term study on children with favorable results (53). A mixture of amino acids and bicarbonate-buffered solutions can also give good results because of better acid buffering and enhanced protein anabolism. Glucose-free APD will possibly be used in the future, using a mixture of glycerol and amino acids during the night and icodextrin during the day for ultrafiltration failure type I. The rationale is that small osmotic agents such as glycerol and amino acids are ideal for good ultrafiltration in short dwells like those of APD, while better ultrafiltration during longer daytime dwells could be obtained with icodextrins. Moreover, a period of glucose-free PD could allow recovery of a membrane with type I ultrafiltration failure (reduction, exhaustion, or glycosylation of aquaporins). Bicarbonate will soon be available inAPD with online mixing of dialysate to avoid carbonate precipitation, as in hemodialysis. However, the bicarbonate solution now available in two-chambered bags may present a satisfactory stability once the two solutions are mixed together. In fact, available studies performed in continuous renal replacement therapies, where peritoneal dialysis solutions are often used, show that a bicarbonate solution with electrolytes and glucose is stable without precipitation for up to 72 hours (54). Future trends can also see catheters overcoming flow limitations with double-lumen catheters specific for continuous-flow APD or recirculated APD performed with a cycler using double pump and on-line mo nitoring of intraperitoneal pressure (55). Downloaded from http://www.pdiconnect.com/ by guest on September 16, 2014 The assessment of individual peritoneal transport, commonly using the PET, is a very important step in selecting patients for a successful APD program. Not all categories of peritoneal transport can reach satisfactory results in terms of treatment adequacy with all APD regimens. From previous studies, treatment adequacy for low-transport patients was 6%, for low-average 31 %, for high-average 53%, and for high 10% (9). Nightly APD (with dry day) -that is, NIPD/ NTPD -can give adequate results only in hightransport patients (9). Moreover, in high transporters, NIPD/NTPD is strictly indicated because it can reduce protein loss, glucose absorption, and fluid retention. CCPD/CTPD is indicated in high-average transport patients. These patients, because of their peritoneal transport, cannot reach adequate clearances with NIPD/NTPD even at high volumes (14,16). With the addition of a long daytime dwell, the efficiency of APD is greatly increased in these subjects and a further increase is achievable with two daytime dwells (9,16,49). The use of tidal modality can increase dialysate flow and reduce drain and fill times. Coupled with larger volumes, it can raise clearances, but always in high or high-average transporters (14,19-22). Moreover, tidal APD can be indicated in cases of catheter malfunction. There are no rational indications for any APD prescription in low-average and low transport patients. These patients , even with high volumes, are unable to reach adequate clearances inAPD because of their slow peritoneal transport (14,16). The only practical indication occurs for patients who must be treated by peritoneal dialysis and who cannot perform CAPD. With no data about peritoneal transport characteristics, APD can be indicated as a first treatment in anuric patients with a big body size (> 80 kg) who cannot reach adequacy targets in CAPD. A continuous APD technique (CCPD2/CTPD2) with large tailored fill volumes would be used. APD as first-choice treatment is also indicated in non self patients, in children, in patients with hernias and leaks, and for lifestyle needs. APD as second treatment can be useful in CAPD patients with burnout or with changes in peritoneal transport characteristics towards a higher degree of peritoneal permeability. In these situations, the APD option can effectively reduce the dropout rate. APD can further reduce the dropout rate because the rate of infectious episodes seems lower with this technique (50) and becauseAPD is generally very well accepted by the patients (5). Moreover, in the future, biosensors can be placed on cyclers for many purposes. The intraperitoneal pressure can be measured continuously for on-line optimization offill volume. Closely linked to the pressure, flow speed can also be measured for on-line optimization of exchange times. In the peritoneal fluid, pO2' pCO2, and pH can be measured for both on-line bicarbonate mixing and acid-base and oximetry monitoring, and is possibly also useful for cases of sleep apnea syndrome. Urea can also be easily monitored on-line, together with the conductivity of the dialysate (in the case of on-line fluid production). Lastly, white blood cells in the dialysate can be monitored on-line for early diagnosis of peritonitis (56). REFERENCES Downloaded from http://www.pdiconnect.com/ by guest on September 16, 2014 1. Diaz-Buxo JA, Suki WN. Automated peritoneal dialysis. In: Gokal R, Nolph KD, eds. The Textbook of Peritoneal Dialysis. Dordrecht: Kluwer Academic Publishers; 1994:399-418. 2. Popovich RP, Moncrief JW, Nolph KD, Ghods AJ, Twardowski ZJ, Pyle WK. 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