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BackgroundIcodextrin is widely used in peritoneal dialysis (PD); however, the safety and efficacy of icodextrin are unclear. In the present study, we performed a systematic review of randomized controlled trials (RCTs) that compared icodextrin and glucose for the once-daily long dwell in PD.MethodsElectronic searches were performed in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to select all eligible studies. Eligible studies, as determined by consensus using predefined criteria, were reviewed, and data were extracted onto a standard form.ResultsIn the 9 RCTs that were identified, patients using icodextrin were found to have much greater net ultrafiltration (UF) and a lower incidence of negative net UF compared to patients using 1.5%, 2.5%, and 4.25% glucose solutions. Additionally, icodextrin has a markedly increased UF efficiency ratio and peritoneal clearance of creatinine and urea nitrogen, but residual renal function was not different from patients using glucose solutions for PD. No significant differences were observed between icodextrin and glucose groups with respect to risk of mortality, peritonitis, and total adverse events. Although rashes occurred significantly more often in icodextrin groups, few differences were noted between icodextrin and glucose groups when withdrawal rates secondary to adverse events were compared.ConclusionsThis meta-analysis suggests that icodextrin provides patients with greater fluid removal and small solute clearance and does not cause any damage to residual renal function. Icodextrin is particularly appropriate for use in patients with high peritoneal transport status.

Background A recent study by Jeloka et al. (Perit Dial Int 2006; 26:336–40) highlighted the high variability in maximum ultrafiltered volume (UFmax) and the corresponding dwell time (tmax) obtained using 7.5% icodextrin solution. We aimed to pinpoint the possible sources of this phenomenon by simulating the icodextrin ultrafiltration (UF) profiles according to the three-pore model of peritoneal transport. Method The individual UF time courses observed in the study by Jeloka et al. ( n = 29) were first characterized by linear and quadratic regression. We were then able to identify four main patterns. These were then adapted to UF profiles generated by the three-pore model by systematically altering the values of some model parameters, namely, the mass transfer area coefficient (MTAC or PS) for icodextrin/glucose, the peritoneal UF coefficient (LpS), the plasma colloid osmotic pressure gradient (ΔΠ), and the macromolecular clearance out of the peritoneal cavity (ClLF). Results Modifications in the PS values caused only marginal variations in UFmax and tmax, while more significant changes were produced by altering LpS and ClLF. However, far more evident was the importance of changes in ΔΠ In fact, lowering ΔΠ to 14 mmHg caused a steady increase in UF with 10 – 14 hour dwells. On the contrary, the UF profiles became nearly “flat” when ΔΠ was increased to 30 mmHg. The parallel shifts induced by altering icodextrin metabolite concentrations did not markedly influence UFmax or tmax. Conclusion The UF pattern in icodextrin dwells seem to be mainly determined by the plasma colloid osmotic pressure, while only moderate changes can be seen with alterations in LpS and ClLF. The result is not completely unexpected considering that icodextrin acts by inducing a strong colloid osmotic gradient. A number of clinical studies would be needed, however, in order to prove this hypothesis.

Objective To validate the use of a modified three-pore model for predicting fluid transport during long dwell exchanges that use a 7.5% icodextrin solution. Design A nonrandomized, single group, repeated measures study. Patients Ten peritoneal dialysis patients underwent a single 8-hour exchange of a 7.5% icodextrin solution. All patients were naïve to icodextrin. Main Outcome Measures A modified three-pore model was used to model solute and fluid transport during each 8-hour exchange. Concordance correlation coefficients were used to estimate the level of agreement between modeled and measured values of net ultrafiltration (UF) and intraperitoneal volume. Methods Each patient underwent a modified 8-hour standard peritoneal permeability analysis using a 2-L 7.5% icodextrin exchange. Dextran 70 was added to the icodextrin solution as volume marker to estimate fluid transport kinetics. Transcapillary UF, fluid absorption, and intraperitoneal volumes were assessed via the volume marker at 0, 5, 15, 30, 60, 120, 240, 300, 360, 420, and 480 minutes. Results There was strong agreement (concordance correlation = 0.9856) between net UF as measured by the volume marker data and net UF as modeled using the modified three-pore model implemented in PD Adequest (Baxter Healthcare, Deerfield, Illinois, USA). Conclusions Net UF and intraperitoneal volumes for long dwell exchanges using a 7.5% icodextrin solution can be accurately modeled with a modified three-pore model. Steady state icodextrin plasma levels are needed to accurately predict net UF for chronic users of icodextrin.

Rationale Standard peritoneal glucose solutions may induce the formation of advanced glycation end products (AGEs). Preliminary data suggest that AGE formation may be less with the use of polyglucose solutions (icodextrin). Therefore, we investigated whether the use of icodextrin for the long dwell would result in a reduction in plasma and dialysate levels of the AGE products N∊-(carboxymethyl) lysine (CML) and N∊-(carboxyethyl)lysine (CEL). Patients and Methods 40 patients were randomized to treatment with standard glucose solutions (1.36%) and icodextrin for the long dwell during a 4-month study period; 32 patients completed the study. CML was assessed by stable isotope dilution/tandem mass spectrometry. Results CML levels in plasma increased significantly in patients treated with icodextrin (0.146 ± 0.056 at start vs 0.188 ± 0.069 μmol/mmol Lys at the end of the study, p < 0.0001) but did not change in the control group (0.183 ± 0.090 vs 0.188 ± 0.085 μmol/mmol Lys). The same held true for CML levels in dialysate (0.28 ± 0.09 at start vs 0.33 ± 0.11 μmol/mmol Lys at the end of the study, p < 0.025). No change was observed in patients treated with the control solutions (0.31 ± 0.11 at start vs 0.31 ± 0.07 μmol/mmol Lys). Conclusion Contrary to the hypothesis, plasma and dialysate levels of CML increased in patients treated using icodextrin for the long dwell.

Objective A pilot study to compare the use of a combination dialysate (7.5% icodextrin / 1.36% glucose) versus icodextrin 7.5% alone for the long dwell in patients on peritoneal dialysis (PD). Design A 4-week, prospective, randomized crossover study. Setting A large regional renal unit providing treatment for a population of 1.7 million. Patients Five patients on continuous ambulatory PD (CAPD) and 3 patients on automated PD. Main Outcome Measurements Long-dwell and 24-hour ultrafiltration volumes, body weight, 24-hour ambulatory blood pressure, and antihypertensive / diuretic tablet count. Results The use of the combination dialysate resulted in an increase in the median (interquartile range) long-dwell ultrafiltration, from 750 (650 – 828) mL to 1000 (889 – 1100) mL ( p < 0.001), and 24-hour ultrafiltration, from 739 (400 – 1623) mL to 956 (700 – 1750) mL ( p < 0.001). Weight, blood pressure, and tablet count remained unchanged. Conclusions The use of the novel combination dialysate resulted in a 33% increase in long-dwell ultrafiltration and a 29% increase in 24-hour ultrafiltration.

ObjectiveConcerns regarding the impact of ultrafiltration failure on peritoneal dialysis and the effect of hypertonic glucose on the peritoneal membrane have lead to a search for alternative dialysates. Computer simulations based on the three-pore theory suggest that a combination of 1.36% glucose and 7.5% icodextrin (glucose polymer) offers an improved ultrafiltration profile. The aim of the present study was to investigate the ultrafiltration profile of this combination fluid.DesignProspective open study comparing 1.36% glucose, 3.86% glucose, 7.5% icodextrin, and the combination fluid (1.36% glucose/7.5% icodextrin).SettingSheffield Kidney Institute, Northern General Hospital, Sheffield, UK.Patients11 patients currently using peritoneal dialysis not previously exposed to icodextrin.Main Outcome MeasureIntraperitoneal volume was measured using a radioisotope dilution method.ResultsThe combination fluid showed a biphasic ultrafiltration profile, with a steep initial increase in intraperitoneal volume, then a maintained plateau phase for the duration of the study dwell (7 hours). The final volume was greater than that with the 1.36% glucose dwell and the 7.5% icodextrin dwell. The fluid was well tolerated by the patients.ConclusionsThese findings are in keeping with computer simulations using the three-pore model. The combination fluid offers an improved ultrafiltration profile, with a final volume similar to 3.86% glucose, while avoiding exposing the peritoneal membrane to high glucose concentrations. It may have a role as a long dwell to optimize ultrafiltration and possibly prolong peritoneal dialysis technique survival.

← Background In the first half of the year 2001, an unusually large number of culture-negative peritonitis episodes occurred in Center A. One patient noticed that his culture-negative antibiotic-resistant peritonitis promptly cleared after inadvertently stopping the use of icodextrin-containing dialysate, but recurred immediately after using icodextrin again. This observation led to the recognition of eight contemporaneous cases of icodextrin-induced culture-negative peritonitis in Center A, and identification of three additional cases in Center B. ← Design Case studies in 12 patients. ← Setting Peritoneal dialysis unit of a university hospital and an affiliated unit (Center A), and a second university hospital (Center B). ← Patients 12 patients on peritoneal dialysis presenting with culture-negative peritonitis. ← Results At presentation, abdominal pain was absent or mild and dialysate leukocyte counts were moderately elevated (approximately 100 – 1500 cells/mm3). Differentiation of the dialysate leukocytes showed a low fraction of neutrophils (approximately 35%). In eight cases, the evidence that the peritonitis was caused by icodextrin was very strong (the clinical picture and laboratory results mentioned above, unresponsiveness to antibiotic therapy, cure after withdrawal of icodextrin, relapse after rechallenge); in 3 patients, the evidence was strong (as in the cases mentioned above, but no rechallenge was performed). Stopping icodextrin promptly relieved the symptoms and normalized the dialysate leukocyte counts. After rechallenge, a relapse invariably occurred, usually within a few days. In one case, the evidence was circumstantial. ← Conclusion Our findings are compatible with icodextrin-induced peritonitis. This entity is characterized by mild abdominal pain at presentation, a moderate dialysate leukocytosis with a low fraction of neutrophils in the differential count, and resistance to antibiotic treatment. Speculations about the pathogenesis of this type of peritonitis include chemical peritonitis due to a contaminating substance or hypersensitivity to icodextrin.

♦ Objective To establish a relationship between peritoneal transport membrane pattern, analyzed by the peritoneal equilibration test (PET), and drained volume using icodextrin (7.5% Ico) and glucose (3.86% Glu) solutions. ♦ Design Thirty peritoneal dialysis patients were submitted to a standard 4-hour PET and divided into 4 transport categories based on dialysate-to-plasma ratio of creatinine (D/Pcr) and dialysate ratio of glucose at 4 and zero hours of the dwell (D4/D0). Patients were asked to perform exchanges for 2 consecutive nights in 10-hour dwells (2 L 3.86% Glu solution on the first night, and 2 L 7.5% Ico solution on the second night). The drained volume was measured and dialysate samples from the overnight exchanges were obtained for β2-microglobulin (B2M) levels. ♦ Results PET classification using D/Pcr showed that 46.6% of the patients were high and high-average transporters, or 23.3% when D4/D0 was used. In spite of this difference, both methods showed significant correlation ( p = 0.0001, r = 0.862). The mean drained volumes were similar for both solutions (for 3.86% Glu, 2696 ± 369 mL; for 7.5% Ico, 2654 ± 424 mL). The high and high-average transport patients classified by D4/D0 achieved a higher ultrafiltration with 7.5% Ico than with 3.86% Glu ( p = 0.0235). When classified by D/Pcr, the difference was not significant ( p = 0.2243). In the low and low-average transport patients classified by D/Pcr, we observed a significantly lower ultrafiltration when 7.5% Ico was used compared to 3.86% Glu solution ( p = 0.0197). Using D4/D0, we saw a tendency toward lower ultrafiltration ( p = 0.0719) in the same group. We then correlated the PET results and the difference between drained volume with 7.5% Ico and 3.86% Glu solution [ΔV (I–G)]. We found a significant negative correlation between D4/D0 and ΔV (I–G) ( p = 0.002, r = –0.5390), and a positive correlation between D/Pcr and ΔV (I–G) ( p = 0.005, r = 0.4932). The levels of B2M obtained with 7.5% Ico were higher than those obtained with 3.86% Glu solution (for 7.5% Ico, 9.47 ± 6.71 μg/vol; for 3.86% Glu, 7.29 ± 4.91 μg/vol; p = 0.004). Furthermore, we found significant correlation between the total amount of B2M obtained with 7.5% Ico solution and D4/D0 ( p < 0.0001, r = –0.4493), and D/Pcr ( p < 0.0001, r = 0.5431). ♦ Conclusion Mean drained volume was similar between the two solution groups. High transporters, as defined by D4/D0, achieved higher ultrafiltration with 7.5% Ico than with 3.86% Glu solution. This is most likely due to the higher number of small pores in the peritoneal membrane. Low transporters, as classified by D/Pcr, achieved lower ultrafiltration with 7.5% Ico than with 3.86% Glu solution. The ΔV (I–G) and the PET results showed significant correlation, confirming that high transporters have a higher ultrafiltration volume with 7.5% Ico. The total B2M mass obtained with 7.5% Ico was greater than with 3.86% Glu solution and significantly higher in the high transport patients, indicating a larger number of small pores. Thus, the ΔV (I–G) could give us an idea of the peritoneal transport pattern in peritoneal dialysis patients.

Background: The issue of icodextrin biocompatibility is somehow ambiguous. Whereas some experimental data point at better bicompatibility of icodextrin compared with high glucose concentration fluid, other reports showed substantial cytotoxic effects upon monocytes and cultured mesothelial cells. The present investigation exposes the first attempt to investigate the biocompatibility issue in an in vivo and in situ setup. Methods: Mice were intraperitoneally injected once a day with the 7.5% icodextrin solution, during 30 consecutive days. Imprints of the mesothelial monolayer covering the anterior liver surface were taken after 2 h, 15 and 30 injections, as well as after recovery periods of 7, 30 and 60 days. Changes on the cell population were evaluated as a function of: density, cell surface area, cell radius, nuclear surface area, number of nucleoli per nucleus, nuclear cytoplasmic index, as well as for prevalence of multinucleation, mitosis, non-viable cells and apoptotic bodies. Additionally, peritoneal dialysis was performed in 3 groups of rats exposed to 4.25% glucose dialysis fluid, 1.1% amino acids solution, or to 7.5% icodextrin. Samples were taken for thiobarbituric acid reactive substances (TBARS) from each group. Results: Mesothelial cell populations of mice exposed to 7.5% icodextrin displayed significantly reduced density, increased cell size, higher increased nuclear/cytoplasmic index, increased numbers of heterogeneous nucleoli, extremely low prevalence of mitosis, atypical mitosis, micronuclei, reduced cell viability as well as a significantly higher prevalence of apoptosis. Rats exposed to the same experimental solution showed significantly higher levels of TBARS (basically malondialdehyde), testifying for an undergoing process of lipid peroxidation. Conclusions: Overall, these results suggest that the 7.5% icodextrin dialysis solution induced, through a mechanism of lipid peroxidation, substantial DNA injury, leading the exposed monolayer to commit protective cellular suicide. Consequently, this information raises some doubts about the safety of 7.5% icodextrin solution in peritoneal dialysis patients.

Objective Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultra-filtration compared with glucose-based dialysis solutions. Colloid osmosis is the most likely mechanism, but studies in rats suggest it is caused by an increase in osmolality due to degradation of icodextrin. Therefore, human spent dialysate was analyzed with high-performance liquid chromatography (HPLC) using gel permeation size-exclusion chromatography. An increasing peak (with a low molecular weight, < 1000 Da) was observed during the dwell. The aim of this study was to quantitate breakdown products of icodextrin (which could explain this peak) and investigate whether there was a relationship with dialysate amylase concentration and dialysate osmolality. Design Long-dwell effluents (dwell time 9.15 – 14.30 hours) obtained from 12 PD patients using a 7.5% ico-dextrin solution during the night were analyzed. The following icodextrin breakdown products were measured: maltotetraose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentaose (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a 6-hour dwell study. Results In the human studies, the median distribution of the sugars in the effluent was G4, 6.7%; G3, 16.5%; G2, 23.1%; and G1, 53.5%. The osmolality in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median contribution of the sugars G2 – G4 was 5.4 mOsm/kg H2O. No correlation was present between dialysate osmolality and duration of the dwell ( r = –0.04, p = 0.91); nor was there a relation between the concentration of G2 and duration of the dwell ( r = 0.50, p = 0.10). No relationship was found between the amount of amylase and the concentration of G2 in the effluent ( r = 0.49, p = 0.10), nor between the total concentration of the sugars G2 – G4 in the spent dialysate and dialysate osmolality ( r = –0.31, p = 0.33). However, a strong correlation was seen between urea concentration and osmolality ( r = 0.85, p < 0.001), and also between sodium concentration and dialysate osmolality in the spent dialysate ( r = 0.92, p < 0.0001). The levels of the sugars G2, G3, and G4 in effluent were higher than in unused dialysate, but lower than or similar to plasma levels. Concentrations of the sugars G5, G6, and G7 were lower in spent dialysate than in unused dialysate, and higher than in plasma. In the rat study, dialysate osmolality increased with the duration of the dwell. A clear relationship was present between osmolality and concentration of the sugars G2 – G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L. Conclusion A 7.5% icodextrin-based dialysis solution used during the long exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependent mainly on concentrations of the small solutes urea and sodium in the effluent. The contribution of icodextrin degradation products was marginal. In the rat, however, a clear relationship was present between osmolality and icodextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the two species can be explained by the very high amylase concentrations in the rat, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.

Objective To study the influence of peritoneal dialysis (PD) solutions on the formation of early glycated products and advanced glycation end-products (AGEs). Design and Patients The formation of both Amadori albumin and AGEs in glucose- and icodextrin-based PD fluids was analyzed in vitro and in peritoneal effluents of continuous cyclic peritoneal dialysis (CCPD) patients. Results Albumin incubated with glucose-based PD fluids showed a time- and glucose concentration-dependent formation of Amadori albumin and AGEs. Aminoguanidine completely inhibited AGE but not Amadori albumin formation. Albumin incubated in icodextrin resulted in the lowest levels of Amadori albumin and AGE. Amadori albumin levels in effluents of 24 CCPD patients (12 glucose and 12 icodextrin for their daytime dwells) were similar. Dialysate samples collected during a mass transfer area coefficient test in 16 CCPD patients (8 glucose, 8 icodextrin) showed an increase in Amadori albumin formation from baseline ( p < 0.0001), without a difference between the groups. In the total group, there was a positive relationship between duration on PD and dialysate Amadori albumin concentration at 240 minutes ( p = 0.03). The Amadori albumin dialysate-to-plasma (D/P) ratio at 240 minutes was 0.82 ± 0.11, and its clearance amounted to 7.71 ± 1.14 mL/min, while the albumin D/P ratio was 0.010 ± 0.003 and its clearance was 0.089 ± 0.017 mL/min. In a peritoneal biopsy of a CCPD patient, Amadori albumin was observed in the mesothelial layer and the endothelium of the peritoneum. Conclusions Using icodextrin-based instead of glucose-based PD fluids can largely reduce the formation of Amadori albumin and AGEs. However, CCPD patients using icodextrin during daytime dwells do not have lower effluent levels of Amadori albumin and AGEs, probably due to the exposure to glucose during their nighttime exchanges. Kinetic studies suggest washout of locally produced Amadori albumin.

Objective To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD). Design Thirty-three male Sprague–Dawley rats weighing between 275 – 300 g were divided into five groups: group C ( n = 6), control rats implanted with a catheter but not dialyzed; group D ( n = 5), diabetic rats implanted with a catheter but not dialyzed; group G ( n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H ( n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I ( n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. Results The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G ( p < 0.001), group C and group H ( p = 0.001), and group C and group I ( p < 0.05). Significant differences were also found between group G and group D ( p < 0.05), and between group G and group I ( p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to-plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 ± 0.01 vs 0.35 ± 0.01, p < 0.05; D/P urea: 0.87 ± 0.03 vs 0.97 ± 0.02, p < 0.05). Conclusions These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Objective To evaluate the safety, efficacy, and biocompatibility of icodextrin (Ico), continuous cycling peritoneal dialysis (CCPD) patients were treated for 2 years with either Ico- or glucose (Glu)-containing dialysis fluid for their daytime dwell (14 – 15 hours). Prior to entry into the study, all patients used standard Glu solutions (Dianeal, Baxter BV, Utrecht, The Netherlands). Design Open, randomized, prospective two-center study. Setting University hospital and teaching hospital. Patients Both established patients and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years or with peritonitis in the previous month, and women of childbearing potential unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study (19 Glu, 19 Ico). Main Outcome Measures Daytime dwell peritoneal effluents were collected every 3 months in combination with other study variables (clinical data, laboratory measurements, dialysis-related data, and urine collection). Peritoneal transport studies were carried out every 6 months. Results In Glu- and Ico-treated patients, peritoneal transport of low molecular weight solutes and protein clearances neither changed during follow-up nor differed between the two groups. Peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen) measured in effluents did not differ between the groups and did not change over time. All these markers showed a dialysate/plasma ratio of more than 1, suggesting local production. Residual renal function remained stable during follow-up and adverse clinical effects were not observed. Conclusions Peritoneal membrane transport kinetics and markers remained stable in both groups over a 2-year follow-up period. Membrane markers were higher in effluents than in serum, suggesting local production. No clinical side effects were demonstrated. Icodextrin was a well-tolerated effective treatment.

Objective To investigate peritoneal defense during icodextrin use in continuous cyclic peritoneal dialysis (CCPD). Design In an open, prospective, 2-year follow-up study, CCPD patients were randomized to either glucose (Glu) or icodextrin (Ico) for their long daytime dwell. Setting University hospital and teaching hospital. Patients Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years, those who had peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients (19 Glu, 19 Ico) started the study. The median follow-up was 16 and 17 months for Glu and Ico respectively (range 0.5 – 25 months and 5 – 25 months, respectively). Outcome Measures Peritoneal defense characteristics and peritoneal dialysis-related infections were recorded every 3 months. Results Total peritoneal white cell count tended to decrease over time in both groups. After 1 year, absolute numbers and percentages of effluent peritoneal macrophages (PMΦs) were significantly higher in Ico than in Glu patients; this difference in the percentage persisted after 2 years. Percentage of mesothelial cells increased over time in Ico patients. The phagocytic capacity of PMΦs decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci ( p = 0.05) and a significant difference for Escherichia coli ( p < 0.05) phagocytosis in favor of Ico patients. PMΦ oxidative metabolism remained stable over time without a difference between the groups. PMΦ cytokine production and effluent opsonic capacity also remained stable over time. Finally, 16 peritonitis episodes in Glu and 14 in Ico patients occurred. Glucose patients had 37 and Ico patients 32 exit-site infections during the study. Conclusion CCPD patients using Ico did equally as well as Glu-treated patients with respect to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, Ico-treated patients did better.

Objective To review all clinical studies and experience gained with icodextrin to date; primarily its use in peritoneal dialysis in patients with end-stage renal failure, but also its use as an intraperitoneal vehicle. Data sources Peer-reviewed original research articles in the literature; abstracts from international scientific meetings; data generated from the compassionate use programme. Study selection All published studies to date are included, some 10–20 studies being included in this review. Data extraction Data have not been specifically extracted from studies; results have been described in the context of overall experience. Results Over ten years of clinical experience with icodextrin have now been accumulated, in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). A small number of patients have received icodextrin for over five years, with no loss of effect. Icodextrin produces sustained ultrafiltration over long dwells while being iso-osmolar, by the process of colloid osmosis. Conclusion Icodextrin represents the first viable alternative osmotic agent to glucose, for use in solutions for peritoneal dialysis. It also has a potential use as a vehicle solution for intraperitoneal drug delivery.

Objective To give a survey of the principles of peritoneal fluid transport in general, followed by an analysis of the effects of icodextrin on the transport of fluid and solutes. Design A review of the literature and of data on the effects of icodextrin in continuous ambulatory peritoneal dialysis (CAPD) patients at the Academic Medical Center, Amsterdam. Results Icodextrin had no effect on the mass transfer area coefficients of low molecular weight solutes. Also no effect was found on the clearances of albumin and larger serum proteins. Due to convective transport, the clearance of β2-microglobulin was greater with icodextrin than with glucose solutions. Icodextrin was especially superior to glucose in the induction of net ultrafiltration during long dwells, during peritonitis, and in patients with ultrafiltration failure caused by a large effective peritoneal surface area. Conclusion Icodextrin has no effect on the permeability characteristics of the peritoneal membrane, but increases convective flow through the small-pore system. As a result, the peritoneal clearance of β2-microglobulin is higher than with glucose-based solutions.lcodextrin is especially indicated for long dwells and in patients with impaired ultrafiltration caused by a large peritoneal surface area, leading to high transport rates of low molecular weight solutes.

Background Optimization of ultrafiltration and preservation of the peritoneal membrane are desirable objectives in peritoneal dialysis (PD) patients. Mixtures of glucose-and non-glucose-based solutions may help to meet both targets simultaneously. Aim To analyze the effects, in terms of ultrafiltration and peritoneal glucose load, of including icodextrin-based dialysate in the nocturnal schedule of patients undergoing automated PD (APD). Method Following a randomized crossover design, 17 APD patients underwent two 10-day study periods under identical prescription (including amino acid-based solution for the night schedule), except for the substitution of 2 L glucose-based dialysate in the nocturnal mixture (control) by a similar amount of icodextrin-based dialysate (icodextrin phase) in one period. Dependent variables included ultra-filtration, sodium removal, peritoneal glucose load, and residual renal function. We measured serum and urine levels of icodextrin metabolites at the end of each phase. Results Ultrafiltration was marginally higher during the icodextrin phase (median 815 vs 763 mL/day, p = 0.07), while peritoneal sodium removal was similar in both phases (74 vs 71 mmol/L/day). Peritoneal glucose load (median 67.5 vs 104.0 g/day, p < 0.005) and absorption (14.0 vs 35.6 g/day, p < 0.005) were lower during the icodextrin phase. Diuresis was also modestly lower during the icodextrin phase (500 vs 600 mL/day, p < 0.05). Serum levels of icodextrin metabolites were moderately higher in the icodextrin phase ( p < 0.005) in patients both on and off diurnal icodextrin. Conclusion Inclusion of amino acid- and icodextrin-based solutions in the nocturnal schedule of APD patients may allow sustained ultrafiltration and sodium removal while significantly reducing the peritoneal glucose load in these patients.

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. Ultra-filtration 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.

Objective The aim of this study was to apply high performance liquid chromatography (HPLC) with modern gel filtration media to determine high molecular weight (HMW) icodextrin fractions and low molecular weight (LMW) icodextrin metabolites in dialysate and plasma in peritoneal dialysis (PD) patients on treatment with icodextrin, and to explore the potential relationships between these compounds, α-amylase activity, and glomerular filtration rate. Design Retrospective study of dialysate and plasma samples from PD patients. Setting Samples were collected at one PD center. Patients Blood and dialysate samples were obtained from PD patients who were subdivided into three groups: patients using only glucose-based peritoneal dialysis fluid (GPDF; GLU group, n = 23), patients studied after the first long dwell with icodextrin-based peritoneal dialysis fluid (IPDF; 1st ICO group, n = 24), and patients who were regular users of IPDF for the long dwells (ICO group, n = 9). Methods LMW icodextrin metabolites [ i.e., maltose (G2), maltotriose (G3), maltotetraose (G4), maltopentaose (G5), maltohexaose (G6), and maltoheptaose (G7)] and HMW fractions were determined in plasma and dialysate using two different gel filtration HPLC methods. Enzymatic hydrolysis with amyloglucosidase to glucose yielded the total carbohydrate content and this was used to validate the HPLC results. α-Amylase activity was determined using a routine method. Results The results obtained by gel filtration HPLC yielded values of LMW metabolites and HMW fractions in plasma and dialysate in agreement with results obtained with enzymatic hydrolysis. HMW fractions were not detectable in plasma. Absorption of icodextrin from the peritoneal cavity during the long dwell (10 – 16 hours) was, on average, 39% of the amount instilled. During the long dwell, there was a relative decrease in the dialysate concentration of the largest HMW fractions (>21.4 kDa). Plasma concentration of the LMW icodextrin metabolites G2–G7 was highest in the ICO group (2.65 ± 0.54 mg/mL) but also higher in the 1st ICO group (1.97 ± 0.57 mg/mL) compared with the GLU group (0.52 ± 0.23 mg/mL). Plasma α-amylase activity was significantly lower in the 1st ICO group and in the ICO group compared with the GLU group. Conclusions Accurate analysis of HMW icodextrin fractions in dialysate and LMW icodextrin metabolites in plasma and dialysate in PD patients can be achieved by gel filtration HPLC with two different columns. This method can be used to study the complex pattern of changes in icodextrin and its metabolites in plasma and dialysate. The finding that HMW icodextrin fractions were not detected in plasma was unexpected, and differs from results of previous studies by other researchers.

All peritoneal dialysis (PD) solutions are designed to remove toxins and water, normalize the blood electrolyte profile, and provide alkali to help maintain acid-base balance. Different formulations, however, may have different effects upon nutrition status. Solutions with 40, as opposed to 35, mEq/l of sodium lactate have been found to promote weight and muscle mass gain and reduce hospitalization in malnourished PD patients. Glucose is varied to produce solutions with different ultrafiltration potential. The glucose absorbed from the PD solution has a protein-sparing effect. The high glucose concentrations necessary for sustained ultrafiltration over a long dialysis dwell, however, often produce appetite suppression and metabolic abnormalities. Solutions formulated with glucose polymers, instead of hypertonic glucose, may provide sustained ultrafiltration over long dwells with lower carbohydrate absorption and perhaps fewer metabolic effects. Amino acids can also be substituted for glucose at relatively low concentrations. A number of studies have shown that amino acids absorbed from the dialysis solution can provide nutritional benefit to malnourished PD patients.