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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 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↗

Adhesion prevention comparing liquid and solid barriers in the rabbit uterine horn model.

OBJECTIVE: The purpose of this study was to assess the ability of four different either solid or fluid barriers to reduce adhesions in an established model of gynecological surgery. STUDY DESIGN: 50 Chinchilla rabbits underwent bilateral deperitonealization and devascularization of the uterine horns (DUH). Afterwards solid membranes of either hyaluronic acid-carboxymethylcellulose (HA-CMC) or lactide-caprolactone-copolymer (LCC) were placed around the injured uterine horns or fluids (icodextrin (ID) or phospholipids (PL)) were intraperitonealy administered. The control group went without protection. After 10 days, adhesions were measured by planimetry. RESULTS: Phospholipids (median 49.8 mm2) significantly reduced adhesion areas in comparison to all other groups: surgical controls (median 230.6 mm2), HA-CMC (median 194.9 mm2), LCC (median 327.1 mm2), and icodextrin (median 242.1 mm2). CONCLUSIONS: These results prove the efficacy of phospholipids to reduce primary adhesion formation in the Chinchilla double uterine horn model compared to HA-CMC, LCC and icodextrin. Future clinical studies are recommended.

Animals↗

Transperitoneal transport of glucose in vitro.

The effect of fluid mixing intensification, damage of mesothelial cells, gentamicin, and icodextrin on the diffusive glucose transport across the peritoneal membrane were evaluated in in vitro studies. A mathematical model of mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient (P). In the control conditions, the rate of glucose transfer from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) remained constant, and the P value at mean was 2,731 +/- 1,493 x 10-4 (cm x s-1). The change of the stirring rate from 5.5 to 11 ml/min increased P values by about 74% for transport direction I-->M and 58% for M-->I, and the change from 11 to 22 ml/min enhanced P at mean by about 42% for both directions. The damage of the mesothelial layer, using sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial to the mesothelial side of the peritoneum by 41% and to the opposite direction by 70%. Addition of icodextrin to the glucose solution increased glucose bidirectional transport at mean by about 14% for I-->M and 24% for M-->I. Furthermore, gentamicin did not change the I-->M transfer, but diminished M-->I transport by about 12%. In conclusion, the reduction of unstirred fluid layers at the mesothelium and the interstitium-fluid interfaces, removal of mesothelium, and addition of icodextrin increased the diffusive glucose transport in vitro; unstirred fluid layers restricted glucose transfer (I-->M) more than the mesothelium; and peritoneal glucose transport, directed from the mesothelial to the interstitial side of the peritoneum, decreased slightly after the addition of gentamicin.

Algorithms↗

Effects of peritoneal dialysis solutions on the secretion of growth factors and extracellular matrix proteins by human peritoneal mesothelial cells.

OBJECTIVE: To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGFbeta1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC). DESIGN: Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFbeta1 1 ng/mL, or different concentrations of icodextrin. VEGF, TGFbeta1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay. RESULTS: Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFbeta1 secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFbeta1 secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFbeta1 1 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. CONCLUSIONS: The present study provides direct evidence that HPMC can secrete VEGF, TGFbeta1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.

Bicarbonates↗

Sodium removal in patients undergoing CAPD and automated peritoneal dialysis.

OBJECTIVES: To compare sodium removal in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) patients, and to identify the main factors that modify Na removal in clinical practice in these patients. DESIGN: Study in three steps. Cross-sectional observational (Study A), and longitudinal interventional (Studies B and C). PATIENTS AND METHODS: First (Study A) we carried out a cross-sectional survey of Na removal in 63 patients on CAPD and 78 patients on APD. Second (Study B), we studied Na removal in 32 patients before and after changing from CAPD to APD therapy. Finally (Study C), we analyzed the impact on Na removal of introducing icodextrin for the long dwell in 16 patients undergoing CAPD or APD. RESULTS: In Study A, total Na removal averaged 210 mmol/day for CAPD patients and 91 mmol/day for APD patients (p < 0.001); Na removal was < 100 mmol/day in 7.1% of CAPD patients and 56.4% of APD patients. Multivariate analysis identified ultrafiltration [B = 125 mmol/day, 95% confidence interval (CI) 110,140], CAPD therapy (B = 60 mmol/day, 95%CI 37, 83), and residual diuresis (B = 51 mmol/L, 95%CI 34, 69) as independent predictors of Na removal (adjusted r2 = 0.76). For APD patients, longer nocturnal dwell times and performing a supplementary diurnal exchange were also independently associated with higher Na removal rates. In Study B, Na removal decreased from 192 to 92 mmol/day (median) after the change to APD (p = 0.02). In Study C, peritoneal Na removal increased from 98 to 148 mmol/day (median) (p = 0.04) after introducing icodextrin. CONCLUSIONS: Standard APD schedules are frequently associated with poor Na removal rates. For any degree of ultrafiltration, Na removal is better in CAPD than in APD. Icodextrin, supplementary diurnal exchanges, and longer nocturnal dwell times improve Na removal in APD. Sodium removal can be estimated from ultrafiltration in patients on CAPD, but must be specifically monitored in patients on APD.

Adult↗

Evaluation of intraperitoneal pressure and the effect of different osmotic agents on intraperitoneal pressure in children.

OBJECTIVES: To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell. DESIGN: IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2 with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m2 and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated. PATIENTS: IPP was established in 30 patients with median age of 4.5 years (range 1.0 - 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 - 10.9 years) and median treatment period of 12 months (range 5.6 - 122.3 months). RESULTS: Mean IPP was 12.0 +/- 6.5 cm H2O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin. CONCLUSIONS: IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.

Adolescent↗

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Steroids, antihistamines and heparin were amongst the first substances to be advocated for adhesion prevention. More recently icodextrin 4%, hyaluronic acid agents and SprayGel have been used. This review aims to evaluate the role of fluid and pharmacological agents in the prevention of adhesions in fertility-conserving gynaecological surgery. OBJECTIVES: To investigate fluid and pharmacological agents for adhesion prevention when used as adjuvants during pelvic surgery. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesion formation after fertility-conserving gynaecological surgery. DATA COLLECTION AND ANALYSIS: Data extraction and analysis was performed independently by two authors (Metwally M and Watson A). Two-by-two tables were generated for dichotomous outcomes and expressed as odds ratios (OR) with 95% confidence intervals (CI). For continuous outcomes a standardised mean difference was used. MAIN RESULTS: There is no evidence of benefit from the use of steroids, dextran or other pharmacological agents in any of the outcomes. The use of hyaluronic acid agents may decrease adhesion formation (OR 0.31, 95% CI 0.19 to 0.51) and prevent the deterioration of pre-existing adhesions (OR 0.28 (95% CI 0.12 to 0.66). There is insufficient evidence for the use of icodextrin 4% or SprayGel as adhesion-preventing agents. None of the studied agents has been shown to improve the pregnancy rate when used as an adjunct during pelvic surgery. AUTHORS' CONCLUSIONS: The current evidence for the use of fluid and pharmacological agents for the prevention of adhesions is limited. There is no evidence on any benefit for improving pregnancy outcomes when pharmacological and fluid agents are used as an adjunct during pelvic surgery. There is insufficient evidence for the use of the following agents: steroids, icodextrin 4%, SprayGel and dextran in improving adhesions following surgery. There is some evidence that hyaluronic acid agents may decrease the proportion of adhesions and prevent the deterioration of pre existing adhesions. However, due to the limited number of studies available, this evidence should be interpreted with caution and further studies are needed.

Anticoagulants↗

Impact of carrier solutions on pharmacokinetics of intraperitoneal chemotherapy.

PURPOSE: In the treatment of gastrointestinal malignancies with dissemination to peritoneal surfaces the principal advantage of intraperitoneal chemotherapy over intravenous chemotherapy is the high drug concentration achieved locally with low systemic toxicity. This advantage can be optimized by maintaining a large area of contact between the chemotherapy solution and the surfaces within the abdomen and pelvis over a prolonged time period. Using a rat model we compared the pharmacokinetics of two drugs infused intraperitoneally, 5-fluorouracil and gemcitabine, in five different carrier solutions. METHODS: A total of 120 Sprague Dawley rats were randomized into groups according to the carrier solution and the drug administered. Rats were given a single dose of intraperitoneal 5-fluorouracil (20 mg/kg) or gemcitabine (12.5 mg/kg) in 0.1 ml/g body weight of each carrier solution. The carrier solutions used varied in their tonicity (0.3%, 0.9% or 3% sodium chloride), or were isotonic and varied in molecular weight (0.9% sodium chloride, 4% icodextrin and 6% hetastarch). With the hypotonic, isotonic and hypertonic sodium chloride solutions, only 5-fluorouracil was used. Each group was further randomized according to the intraperitoneal dwell period (1, 3 or 6 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the blood was sampled using a standardized protocol. The volume of the peritoneal fluid was recorded, and the drug concentrations in the peritoneal fluid and plasma were determined by high-performance liquid chromatography. RESULTS: Measurements of peritoneal fluid volume showed a more rapid clearance of hypotonic and isotonic sodium chloride solutions from the peritoneal cavity as compared to hypertonic sodium chloride and high molecular weight solutions. When comparing the remaining intraperitoneal volumes at 6 h, the differences were statistically significant for both 5-fluorouracil and gemcitabine when hetastarch (P < 0.0001 and P = 0.0004) and icodextrin (P = 0.002 and 0.008) were compared with isotonic sodium chloride solution. Similarly, there was a significant difference in the volumes recorded at 6 h when hypotonic (P < 0.0001) and isotonic sodium chloride solutions (P = 0.0002) were compared with hypertonic sodium chloride solution. The concentrations of chemotherapy in the different carrier solutions varied little. The total amount of drug in the peritoneal cavity decreased with all solutions and more quickly with 5-fluorouracil than with gemcitabine. There was a significant difference in the total intraperitoneal 5-fluorouracil between hypotonic and isotonic sodium chloride solutions at 1 h (P = 0.0003) and 3 h (P = 0.0043), as well as between the isotonic and hypertonic sodium chloride solutions at 1 h (P = 0.03) and 3 h (P < 0.0001). Similarly, there was a significant difference in the total peritoneal gemcitabine at 6 h between icodextrin and isotonic sodium chloride solution (P = 0.01) and between hetastarch and isotonic sodium chloride solution (P = 0.05). There were no significant differences in plasma 5-fluorouracil and plasma gemcitabine concentrations obtained with the five solutions. CONCLUSIONS: These findings show that the clearance of 5-fluorouracil and gemcitabine from the peritoneal cavity can be significantly modified by varying the tonicity or the molecular weight of the carrier solution. Peritoneal fluid clearance was slower with hypertonic sodium chloride and high molecular weight solutions and this resulted in a reduced clearance of chemotherapy. By using a high molecular weight carrier solution the exposure of intraperitoneal cancer cells to gemcitabine was prolonged and drug availability at the peritoneal surface was increased. Similarly, by using a hypertonic carrier solution the exposure to 5-fluorouracil was prolonged and drug availability at the peritoneal surface was also increased.

Animals↗