[Glucose polymer (icodextrin) as a component of fluid for peritoneal dialysis].
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Dialysis Solutions↗
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Optimal use of glucose polymer (icodextrin) in peritoneal dialysis.
The osmotic effectiveness of glucose polymer is now well established. The relative inertness of this macromolecular compound has been the key factor in its success as the first "colloid" osmotic agent in clinical use. In its present form, it produces sustained ultrafiltration for up to 12 hours, and a daily overnight use would obviate the need for hypertonic exchanges, especially 3.86% glucose. In addition, it could be used in automated peritoneal dialysis regimes to enhance ultrafiltration and solute clearance during the daytime. Preliminary reports also indicate that it is beneficial in diabetic patients and in some patients who have lost ultrafiltration. The new "bimodal" formulations look promising, with the potential to replace all the currently used hyperosmolar exchanges with physiological solutions. Although systemic accumulation of glucose polymer breakdown products occurs, it reaches steady-state levels quickly (within two weeks) and remains stable throughout the duration of polymer use. In the long-term study, these levels of maltose and oligosaccharides over three-and-a-half years represent the longest exposure of these substances in uremic patients without any clinical or metabolic adverse effects and provide an important evidence of safety. Future work based on studies that are ongoing suggest that a family of physiological solutions ("bimodal" preparations in iso-osmolar combination) could be available, and the individual's dialysis prescription could be tailored to take into account the ultrafiltration, metabolic needs, as well as the long-term viability of the membrane. Glucose polymer will be a key component of such solutions.
Dextrins↗
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 beta 2-microglobulin (beta 2m) 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 alpha 2-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 TCUFRo-60 min 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 A. This leads to increased clearances of low molecular weight proteins such as beta 2m 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.
Adult↗
Development of a formulation that enhances gene expression and efficacy following intraperitoneal administration in rabbits and mice.
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.
Adenoviridae↗
Peritoneal dialysis: new developments and new problems.
AIMS: To ascertain the incidence of hyponatraemia, and the impact of an icodextrin-based dialysis solution regime on hyponatraemia, in diabetic and non-diabetic patients using peritoneal dialysis (PD). METHODS: Following severe hyponatraemia, resulting in neurological sequelae, in two diabetic patients who were on icodextrin-based PD for established renal failure, we reviewed the results of all our PD patients. Data was gathered retrospectively, from our database and case notes, on plasma sodium, haematocrit, dry weight estimation, plasma albumin and residual renal function. Patients using icodextrin-based solutions were compared with a random selection of patients using dextrose-based peritoneal solutions. We also compared diabetic patients on and off icodextrin with their non-diabetic counterparts using the same dialysis regime. The data were analysed using the paired Student's t-test. RESULTS: Plasma sodium was significantly lower in all patients using icodextrin-based solutions compared with those patients on dextrose-based PD. Plasma sodium was also found to fall in all patients following the initiation of an icodextrin-based PD regime. The fall in plasma sodium was statistically significant in diabetic and non-diabetic patients, but only fell below the laboratory reference range in the diabetic patients. CONCLUSIONS: Icodextrin-based PD is a risk factor for hyponatraemia and may produce clinically relevant symptoms if, as in our two cases, the hyponatraemia is compounded by other factors.
Diabetic Nephropathies↗
Blood glucose overestimation in diabetic patients on continuous ambulatory peritoneal dialysis for end-stage renal disease.
AIMS: Diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) for renal failure depend on glucose analysers for regular monitoring of glycaemic control. We aim to inform health professionals of the potentially dangerous overestimation of blood glucose values by some analysers in patients using Icodextrin for dialysis. METHODS: Twenty-five patients on continuous ambulatory peritoneal dialysis (10 patients on an 8-12-h nocturnal exchange of Icodextrin) had random glucose analysis performed on venous blood using standardized reference laboratory (lab) technique (glucose oxidase GOD-PAP), and simultaneously on capillary blood using the Precision Q.I.D System (glucose oxidase method) and the Advantage meter (glucose dehydrogenase method). RESULTS: The Precision Q.I.D System agreed with the lab results in both the Icodextrin group and the non-Icodextrin group (80-90% of values fell within 20% of the corresponding lab result). In contrast, the Advantage meter agreed with the lab results only in the non-Icodextrin group (95% of values within 20% of the corresponding lab value), and not in the Icodextrin group, where only 5% of the analyser values fell within 20% of the corresponding lab value. CONCLUSIONS: The Precision Q.I.D System, which utilizes glucose oxidase reaction, is safe for use in diabetic patients treated with Icodextrin. All analysers must be cross-checked with the laboratory reference method before use in these patients.
Adolescent↗
Effect of peritonitis on peritoneal transport characteristics: glucose solution versus polyglucose solution.
BACKGROUND: Peritonitis is a common clinical problem and contributes to the high rate of technique failure in continuous ambulatory peritoneal dialysis treatment. The present study investigated the effect of peritonitis on peritoneal fluid and solute transport characteristics using glucose and polyglucose (icodextrin) solutions. METHODS: A four-hour dwell was performed in 32 Sprague-Dawley rats (8 rats in each group), with 131I albumin as an intraperitoneal volume marker. Peritonitis was induced by an intraperitoneal injection of 2 mL lipopolysaccharide (100 microg/mL phosphate-buffered saline) four hours before the dwell. Each rat was intraperitoneally infused with 25 mL of 3.86% glucose [glucose solution control group (Gcon) and glucose solution peritonitis group (Gpts)] or 7.5% icodextrin solution [icodextrin solution control group (Pgcon) and icodextrin peritonitis group (PGpts)]. RESULTS: Net ultrafiltration was significantly lower (by 44%) in the Gpts as compared with the Gcon group, but was significantly higher (by 138%) in the PGpts as compared with the PGcon group. The peritoneal fluid absorption rate, including the direct lymphatic absorption rate, was significantly increased (by 78%) in the Gpts group as compared with the Gcon group. However, the total fluid absorption did not differ between the PGpts and the PGcon groups. The dialysate osmolality decreased much faster in the Gpts group as compared with the Gcon group, resulting in significantly lower (by 9%) transcapillary ultrafiltration in the Gpts group. In contrast, the dialysate osmolality increased faster in the PGpts group as compared with the PGcon group, resulting in higher (by 40%) transcapillary ultrafiltration in the PGpts group. The in vitro increase in dialysate osmolality was also higher in the PGpts group as compared with the PGcon group. The solute diffusive transport rates were, in general, increased in the two peritonitis groups as compared with their respective control groups. CONCLUSIONS: Our results suggest the following: (1) Peritonitis results in decreased net ultrafiltration using glucose solution caused by (a) decreased transcapillary ultrafiltration and (b) increased peritoneal fluid absorption. (2) Ultrafiltration induced by the icodextrin solution appears to be related to the increase in dialysate osmolality (mainly because of the degradation of icodextrin). (3) Peritonitis results in increased degradation of icodextrin and a faster increase in dialysate osmolality and therefore better ultrafiltration, whereas the fluid absorption rate does not change. (4) Peritonitis results in increased peritoneal diffusive permeability.
Animals↗
Peritoneal transport characteristics with glucose polymer-based dialysis fluid in children.
Scarce data are available on the use of glucose polymer-based dialysate in children. The effects of glucose polymer-based dialysate on peritoneal fluid kinetics and solute transport were studied in pediatric patients who were on chronic peritoneal dialysis, and a comparison was made with previously published results in adult patients. In nine children, two peritoneal equilibration tests were performed using 3.86% glucose and 7.5% icodextrin as a test solution. Dextran 70 was added as a volume marker to calculate fluid kinetics. Serum and dialysate samples were taken for determination of urea, creatinine, and sodium. After calculation of the initial transcapillary ultrafiltration (TCUF) rate, it was possible to calculate the contribution of aquaporin-mediated (AQP-mediated) water transport to ultrafiltration for icodextrin and 3.86% glucose and the part of L(p)S (the product of the peritoneal surface area and the hydraulic permeability) caused by AQP. In children, the transport parameters were similar for the two solutions, except for TCUF, which was lower for icodextrin (0.9 ml/min per 1.73 m(2)) as compared with 3.86% glucose (4 ml/min per 1.73 m(2)). Transport parameters were similar in children and adults for glucose, but with icodextrin, TCUF and marker clearance were significantly lower in children. AQP-mediated water flow was 83 versus 50% with glucose (child versus adult; P < 0.01) and 18 versus 7% with icodextrin (P < 0.01). Data indicate that transport parameters in children using icodextrin are similar to glucose except for TCUF. Differences are explained by the absence of crystalloid osmosis and that TCUF was determined after a 4-h dwell. Comparison of transport parameters and peritoneal membrane characteristics between children and adults reveal that there seem to be differences in the amount and functionality of AQP. However, there are no differences in clinical efficacy of this transport pathway because the absolute flow through the AQP is identical in both groups using 3.86% glucose.
Adult↗
Decreased in vitro formation of AGEs with extraneal solution compared to dextrose-containing peritoneal dialysis solutions.
Extraneal peritoneal dialysis (PD) solution (Baxter Healthcare, Deerfield, Illinois, U.S.A.) contains glucose polymer (icodextrin) as an osmotic agent in place of dextrose. We investigated the ability of Extraneal to form advanced glycation end products (AGEs) in vitro compared to standard PD solutions containing dextrose. Extraneal, Dianeal PD-2 [1.5%, 2.5%, or 4.25% dextrose (Baxter Healthcare)], or phosphate buffered saline (PBS) were incubated for 45 days with human serum albumin (HSA) or type IV collagen. AGE formation was measured by spectrofluorometry using excitation at 350 nm and emission at 430 nm. Solutions were also incubated with collagen affixed to plastic, simulating matrix collagen in the peritoneal membrane. In addition, AGE formation was assessed using icodextrin metabolites (maltose, maltotriose, and maltotetraose) at concentrations normally found in the plasma of patients treated using icodextrin. For PD solutions incubated with albumin, the relative order of AGE formation was: 4.25% dextrose > 2.5% dextrose > 1.5% dextrose > Extraneal. For incubations with collagen (in solution or affixed to plastic), AGE formation was greatest for 4.25% dextrose, intermediate for Extraneal and 2.5% dextrose, and lowest for 1.5% dextrose. Incubation of icodextrin metabolites with albumin for 45 days did not result in appreciable AGE formation. These results confirm that solutions containing icodextrin result in less in vitro AGE formation than do high dextrose solutions. The results also suggest that Extraneal may lead to improved solution biocompatibility in vivo.
Glucans↗
Advanced glycosylation end-products in diabetic rats on peritoneal dialysis using various solutions.
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.
Animals↗
Osmotic agents hamper mesothelial repopulation as seen in the doughnut in vivo model.
BACKGROUND: The problem of mesothelial cell injury derived from the use of peritoneal dialysis solutions has been explored deeply. Conversely, the eventual detrimental effects upon mesothelial cell regeneration have awaked less investigative efforts than those focused on injury. OBJECTIVE: To evaluate in the in vivo and in situ rat "doughnut" model of mesothelial repopulation, the eventual effect of peritoneal lavage with Hank's Balanced Salt Solution (HBSS) as well as that of 4.25% glucose and 7.5% icodextrin dialysis solutions. EXPERIMENTAL ANIMALS: 100 Sprague-Dawley albino rats were included in the study. Animals were divided into five groups of 20 rats each: group 1: control at zero time; group 2: sham-injected rats; group 3: rats exposed to HBSS; group 4: rats treated with 4.25% glucose peritoneal dialysis solution; group 5: rats injected with 7.5% icodextrin. METHODS: Selective exfoliation of a ring of mesothelium (width 0.8 mm, diameter 4 mm) covering the anterior surface of the liver was performed in 80 animals. The control zero-time group was used to evaluate the normal density distribution of the mesothelial cells forming the monolayer. The other groups were treated by means of daily sham injections or intraperitoneal infusion of each experimental solution for a period of 30 consecutive days. After a recovery period of 15 days, imprints and biopsies from the monolayer covering the exfoliated area were taken and processed for light microscopy. RESULTS: Macroscopic observation of the abdominal cavity at the end of the 15-day recovery period showed that the prevalence of fibrotic adhesions between the peritoneal exfoliated area and the neighboring diaphragm was 10% forthe sham-injected group, 5% for the HBSS-exposed animals, 85% for the rats injected with 4.25% glucose, and 95% for the icodextrin-treated group. Prevalence of fibrous adhesions in sham-injected animals and rats exposed to HBSS were devoid of statistically significant differences. Conversely, comparison of these groups with results observed in animals treated with the osmotic agents was significant, at the p < 0.0039 level. Regarding density distribution of mesothelial cells observed in imprints, there were no significant differences between the control zero-time and the sham-injected group. This parameter was marginally lower (p < 0.05) in the HBSS-treated rats. Imprints were not taken from animals exposed to glucose or icodextrin because a dense layer of connective tissue replaced the exfoliated mesothelial area. CONCLUSIONS: Observations made in this study support the contention that both osmotic agents, 4.25% glucose and 7.5% icodextrin, substantially restrain the normal process of mesothelial cell repopulation and induce repair by means of connective tissue. The underlying mechanism is most likely sustained oxidative stress.
Animals↗
[Influence of hyaluronan on peritoneal permeability for macromolecules in vitro].
Recent studies pointed out advantages of high-molecular hyaluronic acid (HA) application into dialysis fluids. This molecule is an essential component of peritoneal extracellular matrix. The compound shows antiadhesive properties and participates in restoring of peritoneal integrality and remodeling of peritoneum, which have been changed by prolonged peritoneal dialysis and returning incidents of peritonitis. Influence of HA on transperitoneal transport of large and small molecules is recognized in a little range. The aim of presented studies in vitro was qualification of hyaluronan influence on transport dynamics of the selected macromolecules (albumin 1 g/dL, icodextrin 7.5 g/dL and insulin 0.1 g/dL). Values of the transfer, directed from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) were expressed as coefficient of diffusive permeability P [cm/s]. In the case of each macromolecule, two separate research series of the experiments were done. In the first one transperitoneal transport in the control conditions (120 min) was analyzed, and in the secondtransfer parameters before (15-60 min) and after hyaluronan (0.04 g/dL) application on the mesothelial side of peritoneal membrane (75-120 min) were examined. Stability of albumin and insulin transport (in the case of the both transfer directions) and icodextin passage (only M-->I direction) was observed in the presented studies when we compare the first and the second hours of the experiments. In the opposite direction (I-->M) it was showed an increase of its transport with time by about 50%. The mean values of P +/- SEM amounted to 0,271 +/- 0,056 [x10(-4); cm/s] and 0,315 +/- 0,057 [x10(-4); cm/s] for albumin and 0,145 +/- 0,033 [x10(-4); cm/s] and 0,146 +/- 0,022 [x10(-4); cm/s] for insulin, respectively in the case of I-->M and M-->I directions and 0,194 +/- 0,035 [x10(-4); cm/s] for icodextrin transfer directed from the mesothelial to the interstitial side of membrane. In the opposite direction (I-->M) values of P coefficient amounted to: 0,280 +/- 0,038 [x10(-4); cm/s] in the first experimental hour, and 0,394 +/- 0,046 [x10(-4); cm/s] in the second one. It was observed also asymmetry of glucose polymer passage with I-->M transfer domination. Hyaluronan eliminated this asymmetry. After use this compound the transport parameters of icodextrin were stable for the both I-->M and M-->I directions. Hyaluronan did not change values of diffusive permeability coefficients P in the case of bidirectional transfer of albumin and insulin. The obtained results show, that values of macromolecules transfer across peritoneum in vitro don't depend on their molecular weight and isoelectric points. Dynamics of albumin and insulin transperitoneal passage is stable. Icodextrin transport, directed from the interstitial to the mesothelial side of membrane, predominates transfer in the opposite direction. Hyaluronan modifies dynamics of transperitoneal icodextrin passage, but doesn't influence on permeability of the membrane in the case of albumin and insulin.
Albumins↗
[Influence of new dialysis solutions on clinical results in patients treated with peritoneal dialysis].
Long-term peritoneal dialysis is associated with changes in the peritoneal membrane. Conventional dialysate solutions are bioincompatible because of their low pH, high glucose content, hyperosmolality and increased concentration of glucose degradation products. The development of double-compartment systems has made it possible to separate glucose from the buffer during heat sterilization, resulting in a higher or even physiologic pH of the solution with reduced concentration of glucose degradation products. These new solutions are less toxic for several cell groups and are better than conventional solutions in preserving membrane function, as demonstrated by experiments in rats. Glucose degradation products promote formation of advanced glycation end-products, and plasma levels of these are markedly reduced when double-compartment systems are used. Clinical studies with these more physiologic dialysis solutions have demonstrated better correction of acidosis, less inflow pain, significantly elevated CA-125 dialysate levels and lower concentrations of markers for inflammation and fibrosis in the effluent. In a retrospective study, a lower rate of mortality was observed in patients who were treated using a double-compartment system than in those treated with standard dialysis solution. Amino acids (in the low-molecular-weight range) and icodextrin (in the high-molecular-weight range) are newer osmotic agents that have been developed as alternatives to glucose. Several clinical studies have shown that amino-acid solution improves various nutritional parameters in patients with malnutrition and is more biocompatible than standard glucose solution. Icodextrin is an iso-osmolar dialysis solution. Ultrafiltration takes place via colloid osmotic pressure and is sufficient in all types of peritoneal transport. Clinical studies using icodextrin have shown better fluid control, especially in high transporters, reduced carbohydrate load and fewer patients with ultrafiltration failure compared with those treated with conventional dialysis solutions. However, allergic skin reactions have been observed in up to 10% of patients treated with icodextrin. Icodextrin may induce a fall of sodium plasma levels. Because of cross-reaction with elevated plasma levels of maltose, serum amylase is determined falsely low and glucose (using the glucose-dehydrogenase method) is measured falsely high, but high plasma levels of maltose do not affect measurement of lipase or measurement of glucose using the glucose-oxidase method. New dialysate solutions will have a positive influence on both survival and technical drop-out rates in patients receiving peritoneal dialysis treatment.
Clinical Trials as Topic↗
Effect of intraperitoneal antiadhesive fluids in a rat peritonitis model.
HYPOTHESIS: Phospholipids and icodextrin reduce peritoneal adhesions resulting from general peritonitis without promoting abscess formation. DESIGN: Evaluation of adhesion reduction fluids in a randomized animal study using a standardized peritonitis model. SETTING: Experimental animal model in a university laboratory. INTERVENTIONS: In 60 rats, experimental peritonitis was induced using the cecal ligation and puncture model. On day 1, the abdominal cavity was rinsed with 10 mL of isotonic sodium chloride solution and the cecum was resected. Animals were randomly assigned to 3 groups: the RL group, which received Ringer lactate intraperitoneally; the PL group, which received phospholipids intraperitoneally; and the ID group, which received icodextrin intraperitoneally. In each group, 50% of the animals were humanely killed at day 11 and 50% at day 21. MAIN OUTCOME MEASURES: The areas of adhesions were measured and the abscess formation was scored according to location and size. Abscesses, abdominal fluid, and blood were sampled for microbiologic workup. RESULTS: The median area of adhesions was significantly lower in the PL groups (PL(11), 43.7 mm(2); PL(21), 20.4 mm( 2)) than in the RL groups (RL(11), 163.8 mm(2); RL( 21), 120.9 mm(2)) and ID groups (ID(11), 418.5 mm( 2); ID(21), 218.6 mm(2)). Abscess formation was increased by icodextrin but not influenced by phospholipids, whereas microbiologic investigations did not reveal any differences among these 3 groups. CONCLUSIONS: In this model of general peritonitis, phospholipids significantly reduced adhesion formation without promoting septic complications. Icodextrin enhanced adhesion and abscess formation in this peritonitis model. Phospholipids may be beneficial for adhesion control in general peritonitis.
Abdominal Abscess↗
Sodium sieving in children.
Sodium sieving is a consequence of dissociation between the amount of water and sodium transported over the peritoneal membrane. This dissociation occurs in the presence of aquaporin-mediated water transport. Sieving of sodium can be used as a rough measure for aquaporin-mediated water transport. Icodextrin contains glucose polymers, inducing ultrafiltration by colloid osmosis. Therefore, aquaporins play a minor role in ultrafiltration, which is confirmed by the absence of sodium sieving. Icodextrin is very suitable for the daytime dwell in children on a nightly intermittent peritoneal dialysis regimen. Ultrafiltration obtained with icodextrin is similar to ultrafiltration obtained with 3.86% glucose after a 12-hour dwell. When using icodextrin in children, it is also confirmed by the absence of sodium sieving that the aquaporins play a minor role in ultrafiltration.
Aquaporins↗
A preceding exchange with polyglucose versus glucose solution modifies peritoneal equilibration test results.
The peritoneal equilibration test (PET) is an important tool for evaluating peritoneal membrane characteristics. The polyglucose icodextrin induces ultrafiltration caused by colloid osmosis through the small pores of the peritoneal membrane and therefore is especially effective during long dwell times. The main indications for polyglucose solutions are daytime dwells in patients on automated peritoneal dialysis and nighttime exchanges in continuous ambulatory peritoneal dialysis (CAPD) patients. In CAPD patients, PET is started immediately after the icodextrin exchange. Therefore, we performed two PETs in each of 15 CAPD patients. PET post-1.36% glucose was performed immediately after a preceding exchange with 2 L of 1.36% glucose dialysate solution (dwell time, 10 hours). PET postpolyglucose was started immediately after a preceding exchange with 2 L of 7.5% icodextrin solution (dwell time, 10 hours). The dialysate to plasma (D/P) ratio of creatinine, phosphate, and sodium during PET postpolyglucose was significantly greater than during PET post-1.36% glucose at 1, 2, 3, and 4 hours of dwell time. The quotient of dialysate glucose at 1, 2, and 4 hours of dwell time to dialysate glucose at 0 dwell time was significantly lower in PET postpolyglucose compared with PET post-1.36% glucose. In the case of creatinine, phosphate, and glucose, PET postpolyglucose curves tended to be steeper than those of PET post-1.36% glucose during the first hour of dwell time, whereas both curves were parallel between 1 and 4 hours of dwell time. The course of D/P ratio curves of urea nitrogen, protein, and albumin was nearly identical between PET postpolyglucose and PET post-1.36% glucose. In a subgroup of 5 patients, D/P ratios of creatinine and phosphate were also greater in PET postpolyglucose compared with PET performed after a long dwell with 2.27% glucose solution. Before a scheduled PET, CAPD patients using icodextrin solution during the nighttime should perform their nighttime exchange with conventional glucose solution.
Adult↗
The potential role of advanced glycation end product and iNOS in chronic renal failure-related testicular dysfunction. An experimental study.
OBJECTIVES: To investigate the impact of advanced glycation end products (AGEs) and inducible nitric oxide synthase (iNOS) in chronic renal failure (CRF)-associated testicular dysfunction in an experimental model. In additionally, we examined whether different peritoneal dialysis (PD) fluids could contribute to the elevation in AGE level and iNOS expression in the testes. METHODS: Adult male Wistar rats, 10 and 12 weeks of age and weighing 200-330 g, were divided into 5 groups. Group 1 served as the control group. In group 2, CRF was induced and a peritoneal catheter was implanted, but the dialysis procedure was not performed until the end of the study. In group 3, CRF was induced and PD was performed with dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF rats received dialysis fluids containing 3.86% glucose and icodextrin. Finally, an indwelling catheter was implanted and the dialysis procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin (group 5). Chronic PD began 4 weeks after insertion of the catheter. Each morning, this fluid was drained and 20 ml dialysis fluid, containing either 1.36 or 3.86% glucose, was given intraperitoneally for 4 h in unanesthetized animals. Each evening, 20 ml icodextrin was given for 10 h. The dialysis procedure was performed for 8 weeks. The AGE level was determined from the 5-hydroxymethyl-2-furaldehyde (5-HMF) content of penis samples and iNOS expression was assessed by immunohistochemistry. RESULTS: The elevation of 5-HMF was significant in the testes from groups 2, 3, 4, and 5 when compared with group 1. Furthermore, the differences between groups 2 and 4, 3 and 4, and 4 and 5 were also significant (p < 0.05). Immunohistochemical analysis revealed the presence of iNOS predominantly in the Leydig cells. While iNOS staining was significantly lower in group 1 than in other groups, there were also significant differences between groups 2 and 3, 2 and 4, 2 and 5, 3 and 5, and 4 and 5 (p < 0.05). Finally, a significant statistical correlation was found between the 5-HMF and iNOS levels (r = 0.698, p = 0.001). CONCLUSIONS: The present study identifies, for the first time, a potential role of AGE and iNOS in experimental CRF-associated testicular dysfunction. In addition, we found that PD fluids containing glucose contribute to this effect. These results may lead to a better understanding of the pathophysiological pathway in CRF-related testicular dysfunction.
Animals↗
Influence of convection on the diffusive transport and sieving of water and small solutes across the peritoneal membrane.
The three-pore model of peritoneal membrane physiology predicts sieving of small solutes as a result of the presence of a water-exclusive pathway. The purpose of this study was to measure the diffusive and convective components of small solute transport, including water, under differing convection. Triplicate studies were performed in eight stable individuals using 2-L exchanges of bicarbonate buffered 1.36 or 3.86% glucose and icodextrin. Diffusion of water was estimated by establishing an artificial gradient of deuterated water (HDO) between blood/body water and the dialysate. (125)RISA (radio-iodinated serum albumin) was used as an intraperitoneal volume marker to determine the net ultrafiltration and reabsorption of fluid. The mass transfer area coefficient (MTAC) for HDO and solutes was estimated using the Garred and Waniewski equations. The MTAC of HDO calculated for 1.36% glucose and icodextrin were similar (36.8 versus 39.7 ml/min; P = 0.3), whereas for other solutes, values obtained using icodextrin were consistently higher (P < 0.05). A significant increase in the MTAC of HDO was demonstrated with an increase in the convective flow of water when using 3.86% glucose (mean value, 49.5 ml/min; P < 0.05). MTAC for urea was also increased with 3.86% glucose. The identical MTAC for water using 1.36% glucose and icodextrin indicates that diffusion is predominantly through small pores, whereas the difference in MTAC for the remaining solutes is a reflection of their sieving. The increase in the MTAC of water and urea associated with an increase in convection is most likely due to increased mixing within the interstitium.
Biological Transport↗