Icodextrin Peritoneal Dialysis Solution Research Articles

P1210EFFECT OF ICODEXTRIN OR GLUCOSE PERITONEAL DIALYSIS (PD) SOLUTIONS ON TRIGLYCERIDE AND OLEIC ACID LEVELS IN PD PATIENTS (EXIT TRIAL)

Abstract Background and Aims Dyslipidemia is a major cause of cardiovascular disease (CVD) and CVD incidence is definitely increased according to peritoneal dialysis (PD) vintage. The PD solutions contained glucose may affect on dyslipidemia including hypertriglyceridemia. The oleic acid (OA) content in the erythrocyte membrane was increased in patients with acute coronary syndrome and is significantly higher in PD patients than hemodialysis patients. We conducted this trial for comparing effect of icodextrin or glucose PD solutions on triglyceride and oleic acid levels in PD patients. Method This EXIT trial is an open label, randomized, cross-over multi-center trial. Twenty-two patients were enrolled and 15 patients finished this trial. Glucose group was initially exposed to glucose PD solutions for 6 months and then exposed to icodextrin PD solution for 3 months. Extraneal group was initially exposed to icodextrin PD solution for 3 months and then exposed to glucose PD solutions for 6 months. Results The enrolled patients were aged 63.6 ± 9.5 years old and mean PD duration was 10.8 ± 5.9 months. There were no significant differences of baseline clinical and laboratory data between glucose group and extraneal group. There was no significant decrease of triglyceride levels, erythrocyte membrane OA and monounsaturated fatty acid (MUFA) contents after 3 months exposure of icodextrin PD solution compared to baseline. However, there was a tendency of triglyceride levels decrease (p=0.093) after 3 months exposure with icodextrin PD solution and there was a tendency of triglyceride levels increase (p=0.078) after 3 months exposure with glucose PD solutions compared to baseline levels. Continuous 6 months exposure with glucose PD solution significantly increased triglyceride levels (p=0.041), LDL cholesterol levels, erythrocyte membrane OA (p=0.009) and MUFA compared to baseline levels. Conclusion Continuous exposure of glucose PD solutions may negatively affect on triglyceride and erythrocyte membrane OA contents. Combined use of icodextrin and glucose PD solutions may prevent lipid derangement (ClinicalTrial.gov number, NCT NCT02166359).

Effects of Icodextrin and Glucose Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluids on Effluent Cell Population and Biocompatibility Markers IL-6 and CA125 in Incident Peritoneal Dialysis Patients.

Icodextrin peritoneal dialysis (PD) solution has been shown to increase interleukin-6 (IL-6) levels in PD effluent as well as leukocyte and mesothelial cell count. Mesothelial cells release cancer antigen 125 (CA125), which is used as a marker of mesothelial cell mass. This 1-year prospective study was designed to compare peritoneal effluent cell population, its inflammatory phenotype and biocompatibility biomarkers IL-6 and CA125 between icodextrin (E) and glucose bicarbonate/lactate (P) based PD solutions. Using baseline peritoneal ultrafiltration capacity, 19 stable incident PD patients were allocated either to P only (N = 8) or to P plus E for the overnight dwell (N = 11). Flow cytometry was used to measure white blood cell count and differential and the expression of inflammatory molecules on peritoneal cells isolated from timed overnight peritoneal effluents. Compared to P, E effluent showed higher leukocyte (10.9 vs. 7.9), macrophages (6.1 vs. 2.5) and mesothelial cells (0.3 vs. 0.1)×10(6) /L count, as well as expression of HLA DR on mesothelial cells and IL-6 (320.5 vs. 141.2 pg/min) on mesothelial cells and CA125 appearance rate (159.6 vs. 84.3 IU/min), all P < 0.05. In the E group, correlation between IL-6 and CA125 effluent levels (r = 0.503, P < 0.05) as well as appearance rates (r = 0.774, P < 0.001) was demonstrated. No effect on systemic inflammatory markers or peritoneal permeability was found. Icodextrin PD solution activates local inflammation without systemic consequences so the clinical relevance of this observation remains obscure. Correlation between effluent IL-6 and CA125 suggests that CA125 might be upregulated due to inflammation and thus is not a reliable marker of mesothelial cell mass and/or biocompatibility.

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury

Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (P<0.05) and day 50 after reduction of inflammation (P<0.01), indicating that the 7.5% icodextrin peritoneal equilibration test identifies changes in lymphangiogenesis. The solute transport rate was not affected by suppression of lymphangiogenesis. In human peritoneal dialysis patients, the dialysate to plasma ratio of creatinine positively correlated with the dialysate VEGF-D concentration (P<0.001). VEGF-D mRNA was significantly higher in the peritoneal membranes of patients with ultrafiltration failure, indicating that VEGF-D is involved in the development of lymphangiogenesis in peritoneal dialysis patients. These results indicate that VEGFR-3 is a new target to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy

Application of icodextrin-based peritoneal dialysis fluid (PDF) provides a potential benefit in patients with diabetes and end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD) because of better ultrafiltration capacity and avoidance of direct glucose exposure. We examined the effect of glucose and icodextrin-based PDF on histological alterations of peritoneal membranes. Thirty-two male Wistar rats were divided into four groups: control Wistar rats with non-treated (n = 8), streptozotocin (STZ)-induced diabetic rats with 5/6 kidney ablation (n = 8), STZ-induced diabetic rats with 5/6 kidney ablation injected with a standard lactate-buffered 4.25% glucose-based PDF (Dianeal; n = 8) and STZ-induced diabetic rats with 5/6 kidney ablation injected with 7.5% icodextrin-based PDF (Extraneal; n = 8). Intraperitoneal injection was performed once daily with an instillation volume of 20 ml per injection during 8 weeks. Chronic high-glucose-based PDF exposure resulted in increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression, accumulation of advanced glycation end-products (AGEs), and up-regulation of the receptor for AGE (RAGE), which were ameliorated in the icodextrin-based PDF group. The peritoneal damages, such as neoangiogenesis and submesothelial fibrosis, were significantly reduced in icodextrin-based PDF compared to high-glucose-based PDF. Long-term in vivo exposure to high glucose-based PDF promotes the fibrosing process of peritoneal membranes. Icodextrin-based PDF may be helpful in slowing the PDF-induced deterioration of peritoneal function and prolonging the use of peritoneal dialysis in patients with diabetes.

Effects of New Peritoneal Dialysis Solutions, Pyridoxamine and AT1 Receptor Blocker, on TGF-β1 and VEGF Expression in Rat Peritoneal Mesothelial Cells

Background: Transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF) are involved in peritoneal deterioration in continuous ambulatory peritoneal dialysis. The present study was designed to determine whether new peritoneal dialysis solutions (PDS), pyridoxamine (advanced glycation end products (AGE) inhibitor) or AT1 receptor blocker (ARB), affect the expression of VEGF and TGF-β1 in rat peritoneal mesothelial cells (RPMC). Methods: RPMC were stimulated by phosphate-buffered saline (PBS) as control, Dianeal 1.5% (D 1.5%), Dianeal 2.5% (D 2.5%), Dianeal 4.25% (D 4.25%), Dianeal N 1.5% (N 1.5%), Dianeal N 2.5% (N 2.5%) or Extraneal (Ex). In co-incubation experiments, RPMC were stimulated with N 2.5% including pyridoxamine or olmesartan (ARB). VEGF and TGF-β1 protein and mRNA expression in RPMC were analyzed by ELISA and RT-PCR. Results: Glucose-containing PDS, even N 2.5% diluted twofold with M199 (which contains 1.25% glucose), increased VEGF and TGF-β1 expression in RPMC (p < 0.05). Ex did not inhibit VEGF expression and did not inhibit TGF- β1 expression after 24 h in RPMC. Pyridoxamine and ARB significantly reduced N 2.5%-induced VEGF and TGF-β1 protein and mRNA expression in RPMC (p < 0.01). Conclusions: Neither new pH-neutral, lactate-buffered, low-GDP, two-chamber bag PDS, nor 7.5% icodextrin PDS alone satisfactorily inhibited VEGF and TGF-β1 overproduction in RPMC, but ARB or pyridoxamine effectively inhibited glucose-containing PDS (N 2.5%)-induced overproduction.

Stability of Tobramycin and Ceftazidime in Icodextrin Peritoneal Dialysis Solution

The data describing the compatibility of tobramycin and ceftazidime in icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of this study was to assess the chemical stability of tobramycin and ceftazidime in icodextrin PD solution in polyvinyl chloride containers. Commercially available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each bag. Three bags of tobramycin-icodextrin solution were stored under each of the following conditions: refrigeration (4 degrees C), room temperature (25 degrees C), and body temperature (37 degrees C). Three bags of ceftazidime-icodextrin solution were also stored at each of the respective temperatures. Samples were withdrawn from each bag immediately after preparation and at predetermined intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after preparation). Solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. All samples were immediately frozen (-80 degrees C) after collection and stored prior to assay. Total concentrations of tobramycin and ceftazidime in dialysate fluid were determined by high-performance liquid chromatography. The last time point when tobramycin or ceftazidime concentration was >90% from baseline was used to denote stability. All solutions were clear in appearance and no color change or precipitation was observed during the study. For tobramycin, under refrigeration, a mean of 94.6%+/-2.3% of the initial concentration remained at 336 hours (14 days); at room temperature, 90.5%+/-4.3% remained at 168 hours (7 days); at body temperature, 90.0%+/-8.1% remained at 24 hours. For ceftazidime, under refrigeration, a mean of 98.0%+/-0.3% of the initial concentration remained at 168 hours (7 days); at room temperature, 91.6%+/-2.0% remained at 48 hours; at body temperature, 93.9%+/-1.1% remained at 8 hours. Stability was not assessed beyond these respective time points. Premixed tobramycin-icodextrin PD solution remains stable for 336 hours (14 days) when refrigerated (4 degrees C) and for 168 hours (7 days) at room temperature (25 degrees C). Ceftazidime-icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when stored at 4 degrees C and 25 degrees C. It is recommended that the bags be kept refrigerated whenever possible. Tobramycin-icodextrin solution stored at body temperature was stable up to 24 hours, and ceftazidime-icodextrin solutions up to 8 hours, permitting the practice of pre-warming solutions prior to administration.

Effects of Icodextrin on Insulin Resistance and Adipocytokine Profiles in Patients on Peritoneal Dialysis

Icodextrin peritoneal dialysis solution reportedly benefits patients suffering from metabolic derangement due to glucose load from dialysate. However, the effects of icodextrin on insulin resistance and adipocytokine profile remain unclear. Subjects comprised 14 stable patients on peritoneal dialysis for >6 months. Their mean age was 57 +/- 11 years and the mean duration of peritoneal dialysis was 49 +/- 30 months. Patients were classified into groups according to the index of insulin resistance (index of homeostasis model assessment: HOMA-IR): Group A, HOMA-IR < 2.0 (n = 7); and Group B, HOMA-IR >or= 2.0 (n = 7). Glucose peritoneal dialysis solution was subsequently switched to icodextrin once daily during the night. Changes in HOMA-IR and adipocytokine profiles were examined after three months. The glucose absorption dose tended to decrease in both groups after icodextrin introduction, with significant reductions in Group B. No changes were seen in body mass index, fluid status, peritoneal dialysis dose, residual renal function or fasting plasma glucose levels in either group. Plasma insulin levels were unchanged in Group A, but decreased significantly in Group B. The index of insulin resistance was thus unchanged in Group A (from 1.4 +/- 0.4 to 1.5 +/- 0.8) and significantly decreased in Group B (from 5.9 +/- 2.2 to 3.2 +/- 0.6; P < 0.01). Regarding plasma adipocytokine profiles, no changes were found in plasma leptin, tissue necrosis factor-alpha or total plasminogen activator inhibitor-1 levels in either group. Plasma adiponectin levels were unchanged in Group A, but significantly increased in Group B. Icodextrin solution could ameliorate insulin resistance by decreasing insulin levels due to a reduction in the glucose load and an increase in plasma adiponectin levels.

Rate of Synthetic Oligosaccharide Degradation as a Novel Measure of Amylase Activity in Peritoneal Dialysis Patients

Plasma alpha-amylase activity is elevated in uremic patients but lower in peritoneal dialysis (PD) patients using icodextrin in comparison to healthy controls. We studied the rate by which an exogenous oligosaccharide (maltoheptaose; G7) is degraded ex vivo by amylase in plasma from PD patients treated with glucose or icodextrin PD solutions. Plasma amylase (pancreatic and total) activity and concentration were measured in 11 controls and in PD patients treated with glucose (n = 11) and icodextrin (n = 19). The plasma was spiked with G7 and/or synthetic amylase and the metabolites formed were measured by HPLC following incubation at 37 degrees C for 4 hours. The relationship between amylase activity and amylase concentration was similar in all patients and controls. The G7 degradation rate was slower in plasma from icodextrin patients but it was also reduced in patients using glucose compared with the controls, in spite of the higher amylase activity in the glucose group. Normalization (by spiking) of patient plasma with porcine amylase increased but did not normalize the speed of G7 degradation. At a given endogenous amylase activity level, the efficiency of G7 degradation was similar for both patient groups. An ex vivo model to study the relationship between amylase activity and the actual rate of carbohydrate (represented by G7) breakdown was developed and showed that PD patients using glucose and icodextrin degrade G7 at a slower speed than controls. This suggests that amylase-mediated carbohydrate metabolism is reduced in PD patients. Further clinical studies are needed to confirm if these findings hold true also in other groups of uremic patients with varying degrees of kidney failure, as well as in patients undergoing hemodialysis.

American society of nephrology annual meeting San Diego, California, November 14–19, 2006

American society of nephrology annual meeting San Diego, California, November 14–19, 2006

Stability of Vancomycin in Icodextrin Peritoneal Dialysis Solution

Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. There are few data regarding the long-term stability of vancomycin in icodextrin PD solution. To determine the chemical stability of vancomycin in icodextrin PD solution in polyvinyl chloride containers over a 7 day period at 4, 24, and 37 degrees C. Study samples were prepared by adding 2000 mg vancomycin HCl to commercially available 2.0 L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (5 degrees C), 3 at room temperature (24 degrees C), and 3 at body temperature (37 degrees C). Samples were withdrawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of vancomycin in dialysate fluid was determined by high performance liquid chromatography. Under refrigeration, a mean +/- SD of 99.7% +/- 0.5% of the initial vancomycin concentration remained at 168 hours (7 days). At room temperature, 97.5% +/- 3.4% remained at 168 hours. At body temperature, 94.3% +/- 3.9% remained at 24 hours. Stability was not assessed beyond these time points. Premixed vancomycin-icodextrin PD solutions, whether stored refrigerated or at room temperature, were found to be stable for up to 7 days. However, we recommend that these solutions be kept refrigerated whenever possible. Solutions stored at body temperature were stable for up to 24 hours, permitting the practice of prewarming solutions prior to administration.

Stability of Cefepime in Icodextrin Peritoneal Dialysis Solution

Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. Cefepime may be a suitable antibiotic for the treatment of PD-related peritonitis. The stability of cefepime in icodextrin PD solution has not been examined. To determine the chemical stability of cefepime in icodextrin PD solution over a 7-day period. Samples were prepared by adding cefepime HCl 1000 mg to commercially available 2.0-L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (4 degrees C), 3 at room temperature (20 degrees C), and 3 at body temperature (37 degrees C). Study samples were drawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of cefepime in dialysate fluid was determined by liquid chromatography-tandem mass spectrometry. Under refrigeration, a mean +/- SD of 95.7 +/-4.2% of the initial cefepime concentration remained at 168 hours (7 days). At room temperature, 92.0 +/- 17.9% remained at 48 hours. At body temperature, 92.2 +/- 4.7% remained at 4 hours. Beyond these respective time points, <90% of the initial cefepime concentrations remained. Pre-mixed cefepime-icodextrin PD solutions stored at room temperature were stable for up to 48 hours. However, it is recommended that these be kept refrigerated whenever possible. When refrigerated, cefepime-icodextrin solutions were found to be stable for up to 7 days. Solutions stored at body temperature were stable up to 4 hours, permitting the practice of pre-warming solutions prior to administration.

Ezetimibe

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The March 2003 monograph topics are adalimumab, eletriptan, cyclosporine ophthalmic emulsion, montelukast for allergic rhinitis, and icodextrin peritoneal dialysis solution. The DUE is on adalimumab.

Aripiprazole

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The March 2003 monograph topics are adalimumab, eletriptan, cyclosporine ophthalmic emulsion, montelukast for allergic rhinitis, and icodextrin peritoneal dialysis solution. The DUE is on adalimumab.

Efficacy and safety of a 7.5% icodextrin peritoneal dialysis solution in patients treated with automated peritoneal dialysis

In a randomized, prospective, multicenter study, we compared the safety, efficacy, and metabolic effects of a 7.5% icodextrin solution (Extraneal) with a 2.27% glucose solution for long dwell exchanges in patients undergoing automated peritoneal dialysis. Thirty-nine stable patients on automated peritoneal dialysis were randomized to receive either icodextrin (n = 20) or glucose 2.27% solution (n = 19). The study included a 2-week baseline period followed by a 12-week icodextrin treatment phase and a 2-week follow-up period when switching back to glucose. The average net ultrafiltration during the long dwell period was 278 ± 43 mL/d for the icodextrin group and −138 ± 81 mL/d for the control group (P < 0.001). The higher ultrafiltration volume with icodextrin was associated with higher creatinine (2.59 ± 0.09 mL/min versus 2.16 ± 0.11 mL/min) and urea (2.67 ± 0.09 mL/min versus 2.28 ± 0.12 mL/min) peritoneal clearances for the long dwell (both P < 0.001). Ultrafiltration rate per mass of carbohydrate absorbed was +5.2 ± 1.2 μL/min/g in the icodextrin group and −5.5 ± 2.8 μL/min/g in the glucose group (P < 0.001). In the icodextrin group, there was a decrease in serum sodium and chloride compared with baseline (P < 0.01). Total dialysate sodium removal increased in the icodextrin group from 226.7 mEq to 269.6 mEq (week 12, P < 0.001). Serum α-amylase activity decreased from 103 U/L to 16 U/L (P < 0.001). The total icodextrin plasma levels reached a steady-state concentration of 6,187 ± 399 mg/L after 1 week of treatment. Urine volume and residual renal function were not specifically affected by icodextrin compared with glucose. None of the laboratory changes resulted in any reported clinically meaningful side effect. Icodextrin produced increased, sustained ultrafiltration during the long dwell period, increasing (convective) peritoneal clearance and sodium removal in automated peritoneal dialysis patients. © 2002 by the National Kidney Foundation, Inc.

Computer simulations of ultrafiltration profiles for an icodextrin-based peritoneal fluid in CAPD

The three-pore model of peritoneal transport has the ability to predict ultrafiltration (UF) profiles rather accurately, even when high molecular weight (MW) solutes are employed as osmotic agents in continuous ambulatory peritoneal dialysis (CAPD). In the present simulations, we wanted to assess, for various theoretical perturbations, the UF properties of a peritoneal dialysis (PD) solution with an osmotic agent having an average MW of 20 kD and a "number average MW" of 6.2 kD, which is similar to that of icodextrin (ICO). For a PD solution containing a completely monodispersed 20 kD MW osmotic agent, the degree of UF modeled is much higher than that reported for ICO. Hence, to model the behavior of ICO, we subdivided the ICO molecules into eight or more different MW size fractions. For simulations using six or eight subfractions, we obtained an excellent fit of simulated to reported UF data. More dispersed solutions produced UF profiles similar to that with eight fractions. A 2.05 L 7.5% ICO PD solution, despite being slightly hypotonic, yielded a UF volume of nearly 600 mL in 12 hours, modeled for patients not previously exposed for ICO. After nine hours, the UF volume exceeded that produced by 3.86% glucose. The UF rate and volumes increased in proportion to (1) the ICO concentration, (2) the peritoneal surface area, and (3) the peritoneal UF coefficient, but was almost insensitive to increases in the instilled fluid volume. Simulated for patients previously exposed to ICO, having steady-state plasma concentrations of ICO degradation products, the predicted UF volume at 12 hours was reduced to approximately 400 mL. Employing the three-pore model of peritoneal transport and taking into account the polydispersed nature of ICO, it was possible to accurately computer simulate the UF profiles of ICO in accordance with reported data. The simulations suggest an advantage of using ICO in patients with type I UF failure, where UF with a high-MW osmotic agent will exceed that seen in patients not showing UF failure who are on glucose-based PD solutions.