Icodextrin 7.5% dialysate solution (glucose polymer) in patients with ultrafiltration failure: extension of CAPD technique survival.
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Adolescent↗
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Icodextrin plus glucose combinations for use in CAPD.
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Cross-Over Studies↗
Positive interference of icodextrin metabolites in some enzymatic glucose methods.
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Blood Glucose↗
[Glucose polymer (icodextrin) as a component of fluid for peritoneal dialysis].
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Dialysis Solutions↗
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↗
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↗
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↗
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↗
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↗
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↗
Impact of chronic renal failure and peritoneal dialysis fluids on advanced glycation end product and iNOS levels in penile tissue: an experimental study.
OBJECTIVES: To investigate the impact of chronic renal failure (CRF) on advanced glycation end product and inducible nitric oxide synthase (iNOS) in penile tissue, we examined the advanced glycation end product 5-hydroxy methyl furfural (5-HMF) content and iNOS expression in rats in which uremia had been produced by greater than 85% nephrectomy. In addition, the contribution of peritoneal dialysis (PD) fluids to the elevation of penile tissue 5-HMF levels and iNOS staining scores has been investigated. METHODS: Adult male Wistar rats, aged between 10 and 12 weeks and weighing 200 to 330 g, were divided into five groups that each included 6 animals. The first group served as a control group. In the second group, CRF was induced and a peritoneal catheter was implanted, but PD was not performed. In group 3, CRF was induced and PD was performed using dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF was also induced and PD was performed using 3.86% glucose and icodextrin. Finally, in group 5, without CRF, an indwelling catheter was implanted, and the PD procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin. RESULTS: The elevation in 5-HMF levels and iNOS staining scores in penile tissue from groups 2, 3, 4, and 5 was significant compared with group 1 (P <0.05). The elevation in 5-HMF levels and iNOS staining scores was also significant between groups 2 and 3, 2 and 4, 3 and 4, 3 and 5, and 4 and 5 (P <0.05). Moreover, the correlation between the 5-HMF levels and iNOS staining scores was statistically significant (r = 0.525, P = 0.003). CONCLUSIONS: In the present experimental study, we found that 5-HMF levels and iNOS staining scores were significantly elevated in rat penile tissue in which uremia had been produced compared with the groups without CRF. Additionally, PD fluids containing glucose had an effect on the elevation of penile tissue 5-HMF levels and iNOS staining scores.
Animals↗
Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.
Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.
Colorectal Neoplasms↗