Peritoneal Dialysis International, Vol. 26, pp. 336–340 Printed in Canada. All rights reserved. 0896-8608/06 $3.00 + .00 Copyright © 2006 International Society for Peritoneal Dialysis WHAT IS THE OPTIMAL DWELL TIME FOR MAXIMIZING ULTRAFILTRATION WITH ICODEXTRIN EXCHANGE IN AUTOMATED PERITONEAL DIALYSIS PATIENTS? Tarun K. Jeloka,1 Fevzi F. Ersoy,2 Mahmut Yavuz,3 Krishna M. Sahu,1 Taner Çamsari,4 Cengiz Utas¸,5 Semra Bozfakioglu,6 Çetin Özener,7 Kenan Ates¸,8 Rezzan Ataman,9 Fehmi Akçiçek,10 Tekin Akpolat,11 Ibrahim Karayaylali,12 Turgay Arinsoy,13 Emin Yilmaz Mehmet,14 Gültekin Süleymanlar,2 Dorothy Burdzy,1 and Dimitrios G. Oreopoulos1 ♦♦Background: Icodextrin is increasingly being used in automated peritoneal dialysis (APD) for the long dwell exchange to maintain adequate ultrafiltration (UF). However, the UF reported in the literature varies with different dwell times: from 200 to 500 mL with 12 – 15 hour dwells. In order to maximize UF, it is important to know the relationship between dwell time and UF when using icodextrin in APD patients. With this knowledge, decisions can be made with respect to dwell period, and adjustments to the dialysis prescription can be made accordingly. ♦♦Methods: We prospectively studied this relationship in 36 patients from Canada and Turkey. All patients did the icodextrin day exchange manually after disconnecting themselves from overnight cycler dialysis. Dwell period was increased by 1 hour every week, from 10 to 14 hours. Ultrafiltration was noted for each icodextrin exchange. Mean UF for each week (i.e., dwell period) was compared by repeated measures ANOVA. ♦♦Results: We found no difference in mean UF with increasing dwell time: 351.73 ± 250.59 mL at 10 hours versus 371.75 ± 258.25 mL at 14 hours (p = 0.83). We also compared mean UF between different subgroups and found that males (p = 0.02 vs females) and high transporters (p = 0.04 vs low) had higher mean UF. Further analysis of maximal UF showed no correlation to age, sex, diabetic status, transport category, creatinine clearance, Kt/V, duration on peritoneal dialysis, or duration of icodextrin use. ♦♦Conclusion: Icodextrin-related UF in APD patients is not related to demographic factors and does not increase significantly beyond 10 hours. Perit Dial Int 2006; 26:336–340 www.PDIConnect.com Correspondence to: D.G. Oreopoulos, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8 Canada. [email protected] Received 20 July 2005; accepted 3 October 2005. 336 KEY WORDS: Icodextrin; ultrafiltration; automated peritoneal dialysis. F luid removal is an integral part of any dialysis treatment. In peritoneal dialysis (PD), ultrafiltration (UF) is also correlated with patient survival (1) and technique survival (2): lower UF is associated with poor patient survival, and UF failure is the second most common cause of technique failure. Ultrafiltration failure is commonly seen in high transporters and in patients with recurrent peritonitis (membrane failure). Icodextrin, an iso-osmolar (osmolality 285 mOsm/kg) glucose polymer of high molecular weight (MW 16 800), is beneficial in these situations. It has been shown to produce more UF than standard (1.5%) glucose dialysate (3) and is comparable in UF to hypertonic (4.25%) glucose dialysate over 8 – 12 hours of dwell (4). It has an added advantage over hypertonic solutions because hypertonic solutions have been shown to cause peritoneal membrane damage with long-term use (5). Icodextrin exchanges have been in use for more than a decade now, starting with continuous ambulatory peritoneal dialysis (CAPD), where it was used during the long night dwell (8 – 12 hours); UF was >500 mL (4,6–8). But, with increasing use in automated peritoneal dialysis (APD) patients, where the long day dwell period is prolonged to 14 – 15 hours, reported UF with icodextrin varies from 200 to 500 mL (Figure 1) (8–14). On the other hand, using a three-pore computergenerated model, Rippe and Levin showed UF to increase at least until 17 hours (15). In a retrospective study, however, we observed that UF in APD patients was lower than reported in the literature (13) and decided to validate the findings in a prospective trial. We studied the Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 University of Toronto,1 Canada; Akdeniz University,2 Antalya; Uludag University,3 Bursa; Dokuz Eylül University,4 Izmir; Erciyes University,5 Kayseri; Çapa Medical School,6 Istanbul University; Marmara University,7 Istanbul; Ankara University,8 Ankara; Cerrahpas¸a Medical School,9 Istanbul University, Istanbul; Ege University,10 Izmir; Ondokuz Mayis University,11 Samsun; Çukurova University,12 Adana; Gazi University,13 Ankara; Dicle University,14 Diyarbakir, Turkey PDI MAY 2006 – VOL. 26, NO. 3 Figure 1 — Mean ultrafiltration (in milliliters) with icodextrin at different dwell times (hours) in different studies. Continuous ambulatory peritoneal dialysis = white bars; automated PD = shaded bars. Continuous variables were compared using a series of independent sample t-tests; categorical variables were compared using a series of chi-square tests. Differences in mean UF for the total group were analyzed by repeated measures ANOVA. Differences between the subgroups were analyzed by Friedman test. Differences in maximal UF (maximum UF for that individual, irrespective of dwell time) between the subgroups were compared by Mann–Whitney U test. A series of tests were performed to determine whether any of the demographic factors were significantly associated with maximal UF. Linear regression was used to examine the relationship between continuous demographic factors and maximal UF; independent sample t-tests were used to look at the effects of categorical demographic factors on maximal UF. Correlation between variables was studied by Spearman’s rho. All statistical analyses were done using SPSS 13 software (SPSS Inc., Chicago, Illinois, USA). PATIENTS AND METHODS RESULTS This was a prospective, multicenter, interventional study from six different centers in Canada and Turkey. Inclusion criteria were all APD patients who were on icodextrin day exchange for more than a month and willing to participate in the study following written informed consent. Exclusion criteria were history of peritonitis in the previous 3 months and known chronic liver disease or congestive heart failure. Research ethics board approval was granted for the study. Each patient started the study with icodextrin day exchange with a dwell time of 10 hours and continued the same, daily, for the first week. Their nocturnal cycler PD prescription was continued as before. Due to concerns with flushing and wasting of some icodextrin by the machine for the last fill, all patients did the exchange manually after disconnecting themselves from the overnight cycler. Dwell time was increased for the second and subsequent weeks by 1 hour so that the dwell period for the fifth week was 14 hours. The patients were dry for a short period of the day, depending upon the change in icodextrin dwell time. Daily UF with the icodextrin exchange was measured for each patient and recorded for analysis. For Canadian patients, UF was measured by weighing the drain fluid bag and subtracting the dwell fluid bag, and for Turks, UF was recorded using a 5-L volume container. STATISTICAL ANALYSIS Descriptive statistics are expressed as mean, median, standard deviation, and standard error of the mean. Baseline characteristics of the patients, in separate groups and combined, are shown in Table 1. Mean age of patients was 47.5 ± 13.4 years; 83% were males, 14% were diabetics, and 50% were high and high-average peritoneal transporters. Mean duration of icodextrin use in these patients was 18.1 ± 12.4 months. Two of 36 patients (1 Canadian and 1 Turk) had 1.5-L icodextrin fill volume and the rest had 2-L fill volume. There was no difference in baseline characteristics between Canadians and Turks, except for Canadians having higher Kt/V compared to Turks (p = 0.001). TABLE 1 Baseline Characteristics of Patients Total Canadians Turks p Value N 36 7 29 Age (years) 47.5±13.4 56±16.9 45.4±11.9 0.06 Male gender (%) 83.3 85.7 82.7 1.0a Diabetes mellitus (%) 13.8 28.5 10.3 0.24a TS (H+HA) (%) 50 57.1 48.2 1.0a PD age (months) 51.6±26.1 39.7±15.5 54.5±27.5 0.18 ICO age (months) 18.1±12.4 20±12 17.6±12.7 0.66 Kt/V 2.2±0.53 2.7±0.45 2.0±0.45 0.001 ClCr (L/wk/1.73 m2) 74.8±29.5 93.7±40.9 69.1±23.3 0.16 TS = transport status; H = high transporters; HA = high-average transporters; PD/ICO age = duration on PD/icodextrin exchange; ClCr = creatinine clearance. a Due to small number of patients, Fischer’s exact test was used instead of chi-square test. 337 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 relationship between UF and dwell time with icodextrin in APD patients. OPTIMAL DWELL TIME FOR MAXIMIZING UF JELOKA et al. MAY 2006 – VOL. 26, NO. 3 and transport characteristics (p = 0.38) were also found not significantly associated with maximum UF. DISCUSSION In high peritoneal transporters and patients with membrane failure, and because of concerns with damage induced by hypertonic glucose dialysate (5), the icodextrin exchange is increasingly being used to maintain significant UF. In our clinical practice, we have often noted that net UF in some patients, despite being on icodextrin exchange, is not significant, requiring an additional midday PD exchange (enhanced continuous cycling PD). There is a belief (based on simulation studies) that icodextrin UF keeps increasing with increasing dwell time, but it is better to know the expected UF with an icodextrin exchange and if a longer dwell will result in higher UF. Net icodextrin UF reported in the literature is approximately 500 mL with an overnight dwell of 8 – 12 hours’ exchange on CAPD (4,7,8). In fact, in a computer-generated three-pore model simulating CAPD, Rippe and Levin showed that icodextrin UF keeps increasing, even after a 15-hour dwell (15). In APD patients, most studies have shown that icodextrin UF is around 168 – 270 mL (8–13). However, Finkelstein et al. recently showed mean UF with icodextrin in APD patients to be >500 mL with a dwell TABLE 2 Mean Ultrafiltration (in milliliters) with Icodextrin for Each Week of Increasing Dwell Time Dwell N Meana SD SE Minimum Median Maximum Week 1: 10 hours Week 2: 11 hours Week 3: 12 hours Week 4: 13 hours Week 5: 14 hours 31 35 36 35 35 351.73 348.71 386.63 390.34 371.75 250.59 234.72 240.86 257.68 258.25 45.00 39.67 40.14 43.55 43.65 –330.86 –302.29 –338.00 –388.00 –309.43 312 362 390 376.28 387.42 1126.29 1183.43 1233.43 1240.57 1012.00 a p = NS, between any of the weeks. TABLE 3 Differences in Mean Ultrafiltration (in milliliters) with Icodextrin in Different Subgroups with Increasing Dwell Time (For simplicity, SD has deliberately not been included) Week Week 1 Week 2 Week 3 Week 4 Week 5 Canadians Turks Males Females High transporters Low transporters 343.78 263.11 304.48 302.47 343.13 352.59 370.11 406.45 408.52 378.90 380.38 376.48 418.42 415.99 392.68 232.38 214.46 227.67 266.39 270.58 402.35 390.73 438.40 444.35 421.54 302.65 295.92 286.19 331.38 357.12 Diabetics Nondiabetics 575.51 562.13 530.04 581.66 575.13 p Values between countries (0.162), gender (0.02), transport categories (0.04), and diabetic status (0.07). 338 298.03 304.55 357.94 350.76 329.67 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 Mean UF for the whole group did not show an increase with increasing dwell time, as shown in Table 2. Mean UF did not show a change with increasing dwell time even when patients were divided into subgroups (Table 3). Median intraindividual standard deviation of UF over the 5-week period was 104.3 (39.3 – 356.9), reflecting the day-to-day variation of UF, which was also shown to lack concordance as per Kendall’s test (Kendall’s coefficient of concordance W = 0.044). When weekly UF was analyzed instead of daily UF to control for daily variation, again there was no concordance among weekly average UF during 5 weeks (W = 0.11; Kendall’s W < 0.3 denotes weak or no concordance). On the other hand, the median interindividual SD of UF was 266.9 (224.7 – 333.9), reflecting an even higher variation between individuals. Mean UF was higher in males compared to females and in high transporters (high + high average) compared to low transporters (low + low average), as shown in Table 3. Since mean UF did not differ with increasing dwell time, we tried to compare maximum UF (maximum UF for all individuals irrespective of dwell time) between subgroups and determine its association, if at all, with any of the demographic factors. Maximum UF also did not differ between the subgroups. There was no correlation between maximum UF and age, creatinine clearance, Kt/V, duration on PD, or duration on icodextrin exchange (data not shown). Gender (p = 0.39), diabetes (p = 0.54), PDI PDI MAY 2006 – VOL. 26, NO. 3 teristic, creatinine clearance, Kt/V, duration on PD, or duration of use of icodextrin beyond 1 month. ACKNOWLEDGMENTS We thank Eczacibasi-Baxter Company of Turkey for their support. We also thank Sharron Izatt, Nurse Manager of the University Health Network PD program in Toronto, and all PD nurses in Canada and Turkey for patient care and their support in this study. REFERENCES 1. Brown EA, Davies SJ, Rutherford P, Meeus F, Borras M, Riegel W, et al. Survival of functionally anuric patients on automated peritoneal dialysis: The European APD Outcome Study. J Am Soc Nephrol 2003; 14:2948–57. 2. Wilkie ME, Plant MJ, Edwards L, Brown CB. Icodextrin 7.5% dialysate solution (glucose polymer) in patients with ultrafiltration failure: extension of CAPD technique survival. Perit Dial Int 1997; 17:84–7. 3. Mistry CD, Mallick NP, Gokal R. Ultrafiltration with an isosmolar solution during long PD exchanges. Lancet 1987; ii:178–82. 4. Mistry CD, Gokal R, Peers E, MIDAS Study Group. Randomized multicenter clinical trial comparing isosmolar icodextrin with hyperosmolar glucose solution in CAPD. Kidney Int 1994; 46:496–503. 5. Davies SJ, Phillips L, Naish PF, Russell G. Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis. J Am Soc Nephrol 2001; 12:1046–51. 6. Johnson DW, Arndt M, O’Shea A, Watt R, Hamilton J, Vincent K. Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload. BMC Nephrol 2001; 2:2. 7. Wolfson M, Piraino B, Hamburger J, Morton AR, for the Icodextrin Study Group. A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis. Am J Kidney Dis 2002; 40:1055–65. 8. Finkelstein F, Healy H, Abu-Alfa A, Ahmad S, Brown F, Gehr T, et al., on behalf of the Icodextrin High Transporter Trial Group. Superiority of icodextrin compared with 4.25% dextrose for peritoneal ultrafiltration. J Am Soc Nephrol 2005; 16:546–54. 9. Woodrow G, Stables G, Oldroyd B, Gibson J, Turney JH, Brownjohn AM. Comparison of icodextrin and glucose solutions for the daytime dwell in automated peritoneal dialysis. Nephrol Dial Transplant 1999; 14:1530–5. 10. Posthuma N, Wee PM, Donker AJM, Oe PL, Peers EM, Verburgh HA [The Dextrin in APD in Amsterdam (DIANA) Group]. Assessment of the effectiveness, safety, and biocompatibility of icodextrin in automated peritoneal dialysis. Perit Dial Int 2000; 20(Suppl 2):S106–13. 339 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 period of 14 – 16 hours (8). In contrast, our study showed mean UF with icodextrin dialysate to be about 350 – 400 mL for any dwell time between 10 and 14 hours. Finkelstein’s study does not mention if their patients were naïve for icodextrin, which, if true, can possibly explain the difference in UF, as our patients were on longterm icodextrin exchange. This has also been shown in Rippe and Levin’s computer-simulated model for CAPD patients (15). A search of the literature shows that UF in APD patients with a long dwell (14 – 16 hours) is less than that in CAPD patients with a shorter dwell (8 – 12 hours) (Figure 1) (7–13). In our study, mean UF for a 10-hour dwell in APD patients (not reported before) is only 350 mL, which is much lower than that reported for CAPD with a similar dwell time. Neri et al. studied this aspect of difference and concluded that APD patients have less UF because of increased lymphatic absorption due to increased intra-abdominal pressure from being in an upright posture (16). In our prospective analysis, mean UF did not differ with various dwell times of 10 – 14 hours. Mean UF also remained similar, with no effect of dwell time, in the various subgroups (country of origin, gender, transport characteristics, and diabetic status). This means that, if the nocturnal cycler UF is not adequate, then compensating UF can only be achieved by adding an extra midday exchange, rather than attempting to increase the icodextrin dwell time. Mean UF was higher in males compared to females, and higher in high transporters compared to low transporters. The gender difference needs further study as our study had only 6 females versus 30 males; therefore, the difference could be falsely positive due to the small sample size. The difference between transport characteristics (18 high vs 16 low patients), however, has been substantiated in previous studies (17,18), and our study confirms the observation. We also observed significant daily and weekly intraand interindividual differences in icodextrin UF in our study patients. Since mean UF was similar in all groups, we analyzed further the maximal UF to determine if it had any association with demographic factors. This analysis also showed similar maximal UF between the countries, sex, diabetic status, and transport characteristics. Maximal UF had no correlation to age of the patient, creatinine clearance, Kt/V, PD age, or icodextrin age. 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The relationship between ultrafiltration volume with icodextrin and peritoneal transport pattern according to the peritoneal equilibration test. Perit Dial Int 2002; 22:229–33. 18. Wiggins KJ, Rumpsfeld M, Blizzard S, Johnson DW. Predictors of a favorable response to icodextrin in peritoneal dialysis patients with ultrafiltration failure. Nephrology 2005; 10:33–6. Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 340
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