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Objective To evaluate the efficacy and safety of Adept (4% icodextrin solution) in reducing adhesions after laparoscopic gynecological surgery involving adhesiolysis. Design Multicenter, prospective, randomized, double-blind study comparing Adept with lactated Ringer's solution (LRS). Patient(s) Four hundred two patients randomized intraoperatively to Adept (n = 203) or LRS (n = 199) returned for second laparoscopy within 4–8 weeks. Incidence, severity, and extent of adhesions were determined on both occasions. Main Outcome Measure(s) The primary efficacy measure defined by the Food and Drug Administration was the number of patients achieving clinical success with adhesion treatment. Other measures included incidence and American Fertility Society (AFS) scores. Result(s) Significantly more Adept patients achieved clinical success than did LRS patients (49% vs. 38%). In infertility patients, Adept demonstrated particular clinical success compared with LRS (55% vs. 33%). This was reflected in the number of patients with a reduced AFS score (53% vs. 30%) and in fewer patients with a moderate/severe AFS category score (43% vs. 14%). Safety was comparable in both groups. Most events were related to the surgery, with an increase in transient labial edema in the Adept group. Conclusion(s) This is the first randomized, double-blind trial of an adhesion reduction agent. It demonstrated that Adept is a safe and effective adhesion reduction agent in laparoscopy.

This article reviews published studies related to fluid status of Japanese peritoneal dialysis (PD) patients and its impact on technique and patient survival. In addition, some specifics related to clinical background that potentially influence fluid status are described. According to a multi-center survey conducted in Japan, nearly 25% of Japanese PD patients are overhydrated. Available data indicate that a high salt diet may conceivably play an important role in the pathogenesis of fluid overload in Japanese PD patients, and it in turn negatively impacts patient prognosis. Because of the generally adopted policy among Japanese PD experts to avoid regular use of 3.86% glucose solution, icodextrin solution is now used in more than one third of all patients. Other means of managing fluid overload, such as drug therapy, combination (complementary) therapy with hemodialysis, and low sodium PD solution, are also explored and summarized in this article.

Icodextrin is the only large molecular weight osmotic agent available in peritoneal dialysis solutions. Icodextrin (compared to glucose) has a prolonged positive ultrafiltration because of the slow

Ovarian cancer is the most lethal gynecological cancer, accounting for approximately 14 000 deaths in the United States each year. Recently, gene therapy has become a promising new therapeutic option in the treatment of ovarian cancer, and is currently under intensive clinical investigation utilizing a variety of approaches. Most tumor gene therapy vectors are based on adenovirus type 5. Recent studies, however, have shown that expression of the primary Ad5 receptor, coxsackie-and adenovirus receptor (CAR), is often S300 low on malignant ovarian tumors, thus infection of tumor cells by Ad5 vectors is not efficient. Over the last 5 years we have developed new oncolytic Ad vectors, including chimeric Ad vectors possessing fibers derived from Ad group B serotype 35 (Ad5/35), which use CD46 for uptake into cells. In contrast to the Ad5 receptor, CD46 expression is upregulated in malignant tumors, which enables Ad5/35 vectors to infect malignant tumor cells, including primary ovarian cancer cells, that are refractory to infection with Ad5 vectors. A direct comparison of the oncolytic vector Ad5/35.IR-E1A/TRAIL with an Ad5 vector containing an identical transgene cassette demonstrated the superiority of the Ad5/35 capsid containing vector in infection and lysis of SKOV3-ip1 cells and primary ovarian cancer cells isolated from biopsies. A previous study reported significantly longer persistence of adenovirus in the peritoneal cavity when formulated in icodextrin solution compared to saline and glucose solution. To study the effect of icodextrin on Ad5/35 infection of peritoneal organs, a |[beta]|-galactosidase expressing Ad5/35 vector was injected into mice with pre-established peritoneal tumors derived from SKOV3-ip1 cells. We found that 15% icodextrin and to a lesser degree 4% icodextrin increased transduction of tumor cells and at the same time decreased transduction of liver or spleen cells. Finally we analyzed the anti-tumor effect of intraperitoneal injection of Ad5/35.IR-E1A/TRAIL in a model with SKOV3-ip1-derived peritoneal tumors. We demonstrated that icodextrin greatly increased the antitumor effect of Ad5/35.IRE1A/TRAIL when compared to PBS formulated vector. Half the mice were tumor-free after injection of the oncolytic vector in 15% icodextrin and the remaining tumors demonstrated large areas of necrosis and fibrosis. (Notably, icodextrin without Ad had no effect on tumor growth.) This study provides a basis for the use of Ad5/35-based oncolytic vectors and icodextrin, in an intraperitoneal setting, for the treatment of ovarian cancer. We acknowledge receipt of support and icodextrin material from CGT Corporation and Innovata PLC (formerly ML laboratories).

Objective Leptin and adiponectin, well-recognized adipocytokines, are reported to contribute to the pathogenesis of atherosclerosis. The aim of this study was to elucidate the effects of icodextrin-based dialysis solution on adipocytokine metabolism. Methods In 12 non-diabetic anuric patients on peritoneal dialysis, dialysis solution was changed from glucose-based dialysis solution to icodextrin-based dialysis solution for 6 months. Plasma levels of leptin, adiponectin, lipids (total cholesterol, HDL-cholesterol and triglyceride), insulin, blood glucose and insulin sensitivity index by the homeostasis model assessment (HOMA-IR) were compared before and after the use of the icodextrin solution. Results Plasma leptin level was decreased from 15.6 (2.5-69.0) to 7.3 (2.9-45.9) ng/ml (P = 0.018) and plasma adiponectin level increased from 11.6 (6.2-19.6) to 17.6 (7.8-33.0) microg/ml (P = 0.002). A reduction in plasma insulin level from 33.1 (13.8-54.1) to 19.1 (5.8-37.3) muU/ml (P = 0.009) and HOMA-IR from 8.22 (3.68-15.09) to 5.15 (1.40-13.78) (P = 0.015) was observed. While plasma total cholesterol level remained similar, HDL-cholesterol level increased, from 36.0 (22-45) to 43.5 (30-69) mg/dl (P = 0.008) and the triglyceride level decreased, from 174.0 (140-250) to 116.5 (81-207) mg/dl (P = 0.012). Conclusion Icodextrin-based dialysis solution improves abnormal adipocytokine metabolism, dyslipidaemia and insulin resistance, which are known to be associated with atherosclerosis. These results suggest that the use of icodextrin-based dialysis solution might be useful in preventing atherosclerosis in PD patients. Long-term effects of icodextrin-based dialysis solution on the atherosclerosis in peritoneal dialysis patients should be tested.

Peroperative peritoneal trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative adhesion formation. The same cascade seems to play a role in the process of intra-abdominal tumor recurrence. Icodextrin is a glucose polymer solution that is absorbed slowly from the peritoneal cavity, allowing prolonged "hydroflotation" of the viscera, thereby decreasing adhesion formation. This study evaluated the adhesion-preventing properties of icodextrin and its effect on peritoneal metastasis.Reproducible rat models of peritoneal trauma were used, allowing semiquantitative scoring of adhesion formation or tumor load. In one experiment, peritoneal trauma was inflicted; one group was treated by peroperative intra-abdominal instillation of 7.5% icodextrin, one by instillation of RPMI (placebo), and one had no instillate (controls). In another experiment involving a different model of peritoneal trauma, the coloncarcinoma cell line CC531 was injected intraperitoneally to induce tumor load, again using these three groups.Treatment of peritoneally traumatized rats with icodextrin caused a 51% reduction in postoperative adhesion formation ( P.001). However, peroperative intra-abdominal treatment with icodextrin did not affect intraperitoneal tumor cell adhesion and growth of free intra-abdominal tumor cells in rats with this model of severe peritoneal trauma.A 7.5% icodextrin solution is effective in reducing postoperative adhesions without promoting tumor recurrence and therefore may prove useful and safe in oncologic surgery.

Icodextrin-induced peritonitis: Study of five cases and compar- ison with bacterial peritonitis. Background. An epidemic of aseptic peritonitis related to the presence of peptidoglycan contaminant in some batches of icodextrin solution (Extraneal, Baxter Healthcare Corpora- tion) occurred in Europe in the first six months of 2002. Methods. By case-control study we examined the clinical and biologic features of 5 patients with icodextrin-induced peritoni- tis (group AP) and compared them with 7 patients with bacterial peritonitis (group BP) recruited in our clinical center between January and June 2002. Results. Diagnosis of icodextrin-induced peritonitis was con- firmed in all cases by a positive reintroduction test with con- taminated batches of icodextrin. No recurrence was observed on re-exposure to icodextrin free of peptidoglycan. Skin tests were positive with contaminated icodextrin in 2 of 5 patients, while they were negative with icodextrin solution free of pep- tidoglycan (

Objective Peri-operative lavage and postoperative instillation of a 4% icodextrin solution reduces de novo formation and reformation of peritoneal adhesions following abdominal surgery. This experimental study evaluated the effects of 4% icodextrin treatment on the healing of bowel anastomoses and laparotomy incisions. Materials and methods Female New Zealand White rabbits (weight 2.21–2.77 kg) were randomised by ascending weight to one of 3 surgical treatments, each with 2 termination points (6 groups of 8 animals). The treatments were anastomotic bowel surgery alone or with lavage and postoperative instillation of either 4% icodextrin solution or Lactated Ringer's Solution (LRS). The solutions were coded A and B by the supplier, so that the study personnel were blinded to their identity. After the abdomen was opened, 30 ml of solution A or B was instilled and removed by aspiration prior to surgery. The ascending colon was then transected 5 cm aboral to the ileocaecal junction and the ends anastomosed. During surgery, 5 ml of the solution was applied 4 times at the surgical site, and a further 30 ml was administered and aspirated as a postoperative lavage. Just prior to closure of the abdominal wall, 50 ml of the solution was administered as a postoperative instillate. Duplicate treatment groups were terminated 7 and 21 days after surgery and the anastomotic sites inspected for adhesion and/or abscess formation. In 6 animals per group, an 8–12 cm length of colon including the anastomotic site was removed for measurement of bursting pressure, and a section of the abdominal wall including the incision line was tested for breaking strength. The other 2 animals per group provided tissue for histological analysis of wound healing at the bowel and incision sites. Results There was no significant difference between the 3 treatment groups for any parameter (P > 0.05). Compared with the surgical control at either day 7 or 21 after surgery, the administration of solutions A or B did not affect the formation of abscesses or adhesions, the bursting strength of the bowel, or the tear strength of the abdominal wall incision. Histological assessment of the quality of wound healing showed no differences between treatment groups in inflammatory cell infiltration, fibroblast density, blood vessel formation or collagen maturity. Conclusions The use of a 4% icodextrin solution for peri-operative lavage and postoperative instillation in a rabbit model of bowel anastomotic healing did not result in any difference from either LRS treated or untreated surgical controls.

We conducted a series of experiments to determine if intraperitoneal (IP) delivery of recombinant adenovirus (rAd)-based therapies is improved through carrier vehicle selection, and compared an icodextrin solution (a high molecular weight dextrin with a prolonged peritoneal cavity residence time) with a standardized phosphate buffered saline (PBS) delivery solution. In vitro, comparative adenovirus particle concentration determination (27 h) and bioactivity assay (24h) indicated equivalent compatibility with icodextrin or PBS. In vivo, rabbits treated IP (100 ml) with rAd-betagal 1 x 10(9) P/ml in icodextrin showed improved transgene expression throughout the peritoneal wall compared to rAd-betagal in PBS. In PC-3 tumor-bearing mice treated IP with 5 x 10(9) P/0.5 ml or 1 x 10(10) P/0.5 ml rAd-betagal, transgene expression was significantly enhanced (p < 0.01) with icodextrin compared to PBS in both tumor specimens and peritoneal wall. In subsequent studies we compared prolongation of survival in intraperitoneal PC-3 and MDAH-2774 human xenograft tumor models in nude mice using rAd-p53 in icodextrin or PBS in multi-dose ranging (1 x 10(8) to 1 x 10(10) P) experiments. The icodextrin formulation alone significantly increased rAd-p53 mediated survival (p < 0.05). In animals, these results show that IP rAd gene therapy can be improved with the use of icodextrin, and suggest that prolonged retention and distribution in the peritoneal cavity is an important factor.

Effect of icodextrin on volume status, blood pressure and echocardiographic parameters: A randomized study. Overhydration is a risk factor for hypertension and left ventricular hypertrophy in peritoneal dialysis patients. Recently, a high prevalence of subclinical overhydration was observed in peritoneal dialysis patients. Aim of the present open-label randomized study was to assess the effect of a icodextrin 7.5% solution on fluid status [extracellular water (ECW) bromide dilution], blood pressure regulation (24-hour ambulatory measurements) and echocardiographic parameters during a study period of 4 months, and to relate the effect to peritoneal membrane characteristics (dialysate/plasma creatinine ratio). Forty peritoneal dialysis patients (22 treated with icodextrin, 18 controls) were randomized to either treatment with icodextrin during the long dwell or standard glucose solutions. Thirty-two patients (19 treated with icodextrin, 13 controls] completed the study.The use of icodextrin resulted in a significant increase in daily ultrafiltration volume (744 ± 767 mL vs. 1670 ± 1038 mL; P = 0.012) and a decrease in ECW (17.5 ± 5.2 L vs. 15.8 ± 3.8 L; P = 0.035). Also the change in ECW between controls and patients treated with icodextrin was significant (-1.7 ± 3.3 L vs. +0.9 ± 2.2 L; P = 0.013). The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but significantly related to the fluid state of the patients (ECW:height) (r = -0.72; P < 0.0001). Left ventricular mass (LVM) decreased significantly in the icodextrin-treated group (241 ± 53 grams vs. 228 ± 42 grams; P = 0.03), but not in the control group.In this randomized open-label study, the use of icodextrin resulted in a significant reduction in ECW and LVM. The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but was related to the initial fluid state of the patient.

Fluids commonly used for peritoneal dialysis hold poor biocompatibility vis a vis the peritoneal membrane, basically due to the presence of osmotic agents. When rat mesothelium was exposed to glucose-enriched dialysis solutions for 2 h in vivo, an early and short-lived acceleration of cell life cycle was observed, which, after 30 d of exposure, resulted in a depopulated monolayer of senescent cells. These changes appear to result from persistent oxidative stress due to continuous exposure to high concentration of glucose and to substances generated by the Maillard reaction. Long-term exposure (30 d) of the peritoneal mesothelium to 7.5% icodextrin resulted in a depopulated monolayer consisting mostly of senescent cells, which, additionally, showed atypical nuclear changes and atypical mitosis suggesting DNA damage. These changes coincided with substantial lipid peroxidation, starting immediately after the introduction of the icodextrin solution into the rat's abdominal cavity. So far, the currently used osmotic agents in peritoneal dialysis fluids induce substantial oxidative injury to the exposed monolayer in vivo. Use of high concentrations of glucose results in premature senescence of the exposed cell population. The 7.5% icodextrin dialysis fluid induces through lipid peroxidation substantial genomic damage, which, in turn, sets the biological mechanisms leading to protective cellular suicide in motion.

To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh.Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas.In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy.Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%).Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model.

This article presents the results of two randomized, double-blind, controlled studies conducted to compare the efficacy and long-term safety of icodextrin and 2.5% dextrose for the once-daily long dwell in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).Both studies were active-control comparisons of 7.5% icodextrin and 2.5% dextrose for the once-daily long dwell. The efficacy study was a 4-week evaluation of net ultrafiltration and peritoneal clearances of creatinine and urea nitrogen in 175 CAPD patients. The 52-week study in CAPD and APD patients examined the long-term safety of icodextrin and longer term effects, such as body weight and quality of life.Mean net ultrafiltration (587.2 versus 346.2 mL, P0.001) and clearances of urea nitrogen (4.5 versus 4.1 mL/min, P0.001) and creatinine (4.0 versus 3.5 mL/min, P0.001) were increased significantly with icodextrin. Patients receiving icodextrin had no increase in weight after 52 weeks, in contrast to a weight gain of almost 2 kg in the dextrose group (P0.05). There were significantly fewer patients reporting edema in the icodextrin group compared with the dextrose group (6.3% versus 17.9%, P0.01). There were no statistically significant differences between groups for the incidence and severity of adverse events. There were small decreases in sodium and chloride and increases in alkaline phosphatase with icodextrin.Icodextrin provides patients with greater fluid removal and small solute clearance, no weight gain over 52 weeks, and a decreased risk of edema.

BACKGROUND: Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer’s lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an α-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery. METHODS: Women aged ≥18 years, requiring laparoscopic adnexal surgery (n 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n 53); reformation analysis required one or more baseline adhesion (n 42). Incidence, extent and severity of post-operative adhesions were assessed at secondlook laparoscopy after 6–12 weeks. Procedures were video-taped for third party, blinded assessment. RESULTS: Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance. CONCLUSIONS: In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.

Background We evaluated the effect of icodextrin on peritoneal permeability and inflammation in an experimental chronic peritoneal dialysis (PD) model with repeated dwell studies (DSs) in non uremic rats. Methods Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) ( n = 11) or icodextrin 7.5% ( n = 12). After 10 days (DS1) and 21 days (DS2), a 4-hour DS using 30 mL icodextrin solution was performed in conscious animals. Radioiodinated serum albumin (RISA) was used as a macromolecular volume marker. Blood samples were drawn before the start of the dwell and at its end. Results We observed a steady increase in intraperitoneal volume (IPV) versus dwell time (0 – 240 minutes) during DS1 and DS2 in both groups. No significant differences in peritoneal permeability to solutes were observed between the groups. However, in both groups, IPV volume was significantly higher during DS2 after the 4-hour dwell time [IPV icodextrin: 34.4 ± 1.4 mL (DS1), 35.4 ± 1.1 mL (DS2), p < 0.002; IPV Dianeal: 34.2 ± 0.9 mL (DS1), 35.2 ± 0.7 mL (DS2), p < 0.01]. Conclusion Changes of peritoneal permeability seen during in vivo experimental models of chronic peritoneal dialysis in rats with repeated dwell studies are comparable to results obtained in humans on continuous ambulatory peritoneal dialysis (CAPD).

Intra-abdominal adhesion formation causes significant post-operative morbidity. Controlled studies using animal models have been carried out to assess the tolerability and preventive efficacy of icodextrin solution (a biodegradable, biocompatible, glucose polymer). Reduction of adhesion formation was first evaluated in a rabbit double uterine horn model, applying 10-75 ml of 7.5 and 20%, or 50 ml of 2.5-20% icodextrin solution post-operatively. Significant increases in adhesion free sites (P0.005) were observed with volumesor =25 ml, and at concentrationsor =4%. Efficacy of 50 ml 4 and 20% icodextrin was then evaluated both during and after surgery, demonstrating significant reductions in adhesion formation (P0. 002). In one study, intra- plus post-operative use of 4% icodextrin produced the greatest reduction of non-surgical site adhesions; in others, the post-operative effect was predominant. Post-surgical administration of 50 ml 4% icodextrin in a rabbit sidewall model also resulted in more adhesion-free animals, and a significant reduction (P0.001) in areas of adhesion formation and reformation. In a rat infection potentiation model, 4% icodextrin produced no difference in mortality, abscess formation or overall abscess score. These data suggest that 4% icodextrin offers a well-tolerated and effective means of reducing post-surgical adhesion formation.

which can, over time, lead to loss of ultrafiltration capacity [1‐4]. The latter may be related to the use of Background and methods. Icodextrin 7.5% is an isohyperosmolar glucose solutions, which have inadosmolar, glucose polymer-containing peritoneal diaequate biocompatibility. lysis solution with an ultrafiltration potential similar Glucose-based dialysis fluids are particularly suited to glucose 3.86%. We compared in an open, random- for short dwells, since they achieve optimal ultrafiltraized, prospective study the ultrafiltration potential of tion over 4‐6 h. The long daytime dwell in automated icodextrin with that of glucose during the daytime peritoneal dialysis (CCPD) exceeds this optimum by dwell of 23 patients treated with automated peritoneal about 10 h, resulting in limited or even negative ultradialysis (CCPD). filtration during the daytime dwell. Consequently, some Results. Daytime ultrafiltration volume and 24-h ultra- CCPD patients leave their peritoneum dry during the filtration volume increased significantly in icodextrin- day. However, this strategy significantly reduces the treated patients (n=11) at 3 and 6 months, allowing solute clearance, and therefore compromises dialysis patients a less rigid fluid restriction or an adapted adequacy [5]. treatment schedule. This improved the patients’ sub- Loss of ultrafiltration is an important cause of jective well-being. Although ultrafiltration at 9 and 12 treatment failure in long-term peritoneal dialysis months also increased it did not reach statistical patients. Recently, the use of an iso-osmolar glucose significance. Similar to the gain in ultrafiltration polymer solution was advocated in order to maintain volume, 24-h dialysate creatinine clearance per 1.73 m2 adequate ultrafiltration in CAPD patients [6 ]. This (D Cl /1.73 m2) and D Cl /1.73 m2 per litre used dialysate may even extend CAPD technique survival in patients (D Cl /1.73 m2/l ) increased in icodextrin-treated patients. that have failing ultrafiltration when using glucose D Cl /1.73 m2/l per litre ultrafiltrate ( D Cl /1.73 m2/l/UF ) monomer solutions [7]. did not increase. No side-effects of icodextrin were Icodextrin is a glucose polymer of weight average encountered, although serum disaccharide levels molecular weight (Mw) 16 200 dalton and number increased. average molecular weight (Mn) of 5 800 dalton. Conclusion. Icodextrin enhances ultrafiltration during Icodextrin 7.5% contains a glucose polymer chain the daytime dwell in CCPD patients. As a result of an length varying between 4 and 250 glucose units. The increased 24-h ultrafiltration volume, D Cl /1.73 m2 and total osmolality of 7.5% icodextrin solution is 282 D Cl /1.73 m2/l improve. D Cl /1.73 m2/l/UF does not rise, mOsm/kg, pH is 5.3 [8]. Potentially, the iso-osmolar which suggests that the increase in D Cl /1.73 m2 and icodextrin may be less damaging to the peritoneum and the local host resistance compared to the hyperosD Cl /1.73 m2/l is caused by convective transport. molar [346‐486 mOsm/kg) glucose solutions currently used [6,9]. In the present study we investigated the

This experimental study was designed to compare the effects and costs of 4% icodextrin and hyaluronic acid in intraabdominal adhesion formation in rats. This study included 30 healthy Wistar albino rats, each weighing 250-300 gr. Following cecal-ileal abrasion to rats in each group, the following treatments were applied: Group 1 (control, n:10) 5 ml saline irrigation; Group 2 (n:10) 5 ml 4% icodextrin solution; Group 3 (n:10) 3 ml auto-crosslinked hyaluronic acid gel. After 14 days, following a second operation, adhesion intensity scoring, histopathological assessment (inflammation, fibrosis) and costs were compared between groups. The lowest postoperative adhesion intensity score was found in the group 3 and the highest score was found in the group 1 (p=0.028). Group 3 had a non-significantly lower adhesion intensity score than group 2 (p>0.05). In terms of inflammation and fibrosis, group 2 had the lowest score, but there were no significant differences between all the groups (p>0.05). In terms of cost, 4% icodextrin is less expensive than hyaluronic acid. The results demonstrated that both hyaluronic acid and 4% icodextrin are similarly effective in reducing postoperative intraabdominal adhesions. In addition, 4% icodextrin is more cost-effective, which can be an advantage for clinical studies.

Epithelial to mesenchymal transition (EMT) is an important etiologic factor for the development of peritoneal fibrosis in CAPD patients. Mesothelial cells are main source of trans-differentiated fibroblasts under stress from the bioincompatible peritoneal dialysate. In our study there was no difference in dialysate TGF- and VEGF between the low and high GDP groups during an initial 12 months. However, after adjusting with D-CA125, the low GDPs group showed a significantly lower D-TGF-/D-CA125 and D-VEGF/CA125 during the initial 12 months. Among the adjusted peritoneal growth factors for CA125, VEGF/CA125 and TGF-b/CA125 were factors significantly associated with greater EMT in this study. Adjustment of the peritoneal growth factor for effluent CA125 (surrogate for mass of HPMCs) revealed significant association with EMT suggesting that the fibroblastoid transition from HPMCs could be affected by the amount of intraperitoneal growth factors (TGF-b, VEGF) per unit mass of HPMCs. There was significant improvement in both cell score and D-CA125 at the sixth and 12th months after switching from a high GDPs solution to a low GDPs solution. Use of icodextrin solution in patients who had average peritoneal transport showed not only better systemic effects such as decreased glucose absorption via dialysate but also preservation of the peritoneum, including less EMT and high mesothelial bulk mass. In conclusion, Therapy with low GDP solution including icodextrin may positively impact preservation of the peritoneal membrane integrity and prevention of peritoneal fibrosis with time on PD.

The potential of a starch-derived glucose polymer (molecular weight 16 800) as an osmotic agent for peritoneal dialysis was evaluated. A dialysate isosmotic to uraemic serum (302 [SEM 1.3] mOsm/kg) containing 5% glucose polymer (9.4 mmol/l) was compared with hypertonic (332 [1.0] mOsm/kg) 1.36% glucose (76 mmol/l) solution for ultrafiltration, solute transport, and carbohydrate absorption over 6 h and 12 h peritoneal dialysis exchanges. Glucose polymer solution produced substantially greater net ultrafiltration than glucose, while maintaining stable dialysate osmolality throughout the exchanges. At 6 h and 12 h, 14.4% and 28.1% of glucose polymer had been absorbed, compared with 61.5% and 83.0% of glucose; thus, glucose polymer provided less than 50% of the calorie load of the glucose dialysate per unit volume of ultrafiltrate. There was a 7-9-fold increase in serum maltose with glucose polymer. This high-molecular-weight glucose polymer produced sustained ultrafiltration even when dialysate osmolality remained within the physiological range, by a mechanism resembling "colloid" osmosis. It is a safe and effective osmotic agent but its long-term effects need further study.

A randomized multicenter clinical trial comparing isosmolar Icodextrin with hyperosmolar glucose solutions in CAPD. The osmotic effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel “colloid” osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline period. The mean (± SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 ± 36 vs. 150 ± 47 ml; 95% confidence interval (CI) for the difference +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 ± 44 vs. 101 ± 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) and no different from that of 3.86% glucose at eight hours (510 ± 48 vs. 448 ± 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 ± 44 vs. 414 ± 78 ml, 95% CI for the difference -47 to +325 ml; P = 0.06). The biochemical profiles were no different in the two groups except for a small fall in serum sodium (140 to 136 mmol/liter) and chloride (103 to 99 mmol/liter) concentrations in the Icodextrin group. The mean serum maltose increased from a pre-dialysis value of 0.04 g/liter to a steady state level of 1.20 g/liter within two weeks and remained stable throughout the study. This was not associated with any adverse clinical effects and the overall CAPD-related symptom score was significantly better for D than C. This study demonstrates that the daily overnight use of an isosmolar Icodextrin solution was safe and effective up to six months and could replace the overnight use of hyperosmolar glucose solutions. Longer term data will be necessary to establish further safety and efficacy.

Peritoneal transport characteristics with glucose polymer based dialysate. Dialysate fluids containing glucose polymers as osmotic agent are different from the conventional solutions, because they are iso-osmotic to plasma and produce transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the effects on fluid and solute kinetics, a comparison was made between a 7.5% glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based dialysate in 10 stable CAPD patients. In each patient three standard peritoneal permeability analyses (SPA) were done with the osmotic agents and concentrations mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased linearly in time in the icodextrin tests, whereas a hyperbola best described the glucose profiles. The effective lymphatic absorption rate with icodextrin was similar to the glucose based solutions. Mass transfer area coefficients of low molecular weight solutes with icodextrin were also similar to the values obtained with glucose, as was D/P creatinine. A positive correlation was present between the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which was absent in the glucose SPAs. This suggests that in patients with a larger effective peritoneal surface area, more ultrafiltration can be achieved by glucose polymer solutions. Clearances of β2-microglobulin (β2m) were higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P < 0.05). No differences were found for the larger serum proteins albumin, IgG and α2-macroglobulin. Initial D/PNa+ was higher (0.96) with icodextrin than with the glucose based solutions (0.92), due to the higher Na+ concentration of icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of 1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86% glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration coefficient (UFC) of the total peritoneal membrane was assessed using 3.86% glucose (0.18 ± 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed using icodextrin (0.06 ± 0.008 ml/min/mm Hg). The difference between these represented the UFC through the transcellular pores, which averaged 50.5% of the total UFC, but with a very wide range (0 to 85%). An inverse relation existed between the duration of CAPD treatment and the total ultrafiltration coefficient (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the UFC of the small pores (r = -0.48, NS). The TCUFR0–60min through the transcellular pores correlated with the sodium gradient, corrected for diffusion, in the first hour of the dwell (r = 0.69, P < 0.04), indicating that both parameters indeed measure transcellular water transport. It can be concluded that the glucose polymer solution induced sustained ultrafiltration and had no effect on peritoneal membrane characteristics. In addition, the results of the present study support the hypothesis that the glucose polymer solutions exerts its osmotic pressure across intercellular pores with radii of about 40 Å. This leads to increased clearances of low molecular weight proteins such as β2m that are transported through these pores without sieving of Na+. The latter, as found during 3.86% glucose dialysate, is probably caused by transcellular water transport. The transcellular water transport accounted for 50% of the total ultrafiltration with glucose based dialysis solutions. It was lower in long-term CAPD patients.