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PubMed2004

Effect of icodextrin on transperitoneal uric acid and albumin transport in vitro.

In the present study, we compared the influence of icodextrin (2 g/dL) on uric acid (20 mg/dL) and albumin (1 g/dL) transfer through isolated rabbit parietal peritoneum. In separate series of experiments, we used a mathematical model to calculate the transport rate of solutes from the interstitial to the mesothelial side of peritoneal membrane (I --> M) and in the opposite direction (M --> I) before and after introduction of glucose polymer. In control conditions, the rates of uric acid and albumin passage across the rabbit peritoneum remained constant. Mean values [x +/- standard error of the mean (SEM)] of the diffusive permeability coefficient P were 1.936 +/- 0.324 (I --> M) and 2.078 +/- 0.186 (M --> I) for uric acid and 0.341 +/- 0.066 (I --> M) and 0.389 +/- 0.084 (M --> I) for albumin (all x10(-4) cm/s), respectively. The introduction of glucose polymer into the experimental system did not alter the I --> M transport of either solute; but, in the opposite direction, it caused a 17% decline in the P for uric acid (p < 0.05), and an increase of 77% in the same parameter for albumin (p < 0.03). Hence, I --> M transfer dominated M --> I transfer of uric acid (p < 0.04). In contrast, in albumin transport, M --> I was higher than I --> M (p < 0.02). We conclude that, in vitro, icodextrin modifies the diffusive permeability of the peritoneum and induces transport asymmetry for some small and large solutes.

Albumins↗
PubMed2004

Use of bicarbonate/lactate-buffered dialysate with a nighttime cycler, associated with a daytime dwell with icodextrin, may result in alkalosis in children.

The aim of peritoneal dialysis (PD) remains to deliver "appropriate" renal replacement therapy, including sufficient ultrafiltration, correction of acid-base balance, and adequate dialysis dose. We switched our pediatric patients on automated PD from standard lactate-buffered glucose solution (Dianeal: Baxter Healthcare SA, Castlebar, Ireland) to bicarbonate/lactate-buffered solution (Physioneal: Baxter Healthcare SA) as soon as it became available in our country. We also decided to deliver "optimal" dialysis in children by prescribing a long daytime dwell with icodextrin solution (Extraneal: Baxter Healthcare SA). But, adding those three benefits together--APD, Physioneal, and a long dwell with icodextrin--the result, at least in children, was a possible overcorrection of acidosis and an evolution to alkalosis. Thought must be given to developing solutions with varying bicarbonate concentrations for various treatment modalities.

Alkalosis↗
PubMedDate not supplied

Glycation and advanced glycation end-product formation with icodextrin and dextrose.

OBJECTIVE: To review protein glycation and advanced glycation end-product formation with particular reference to its occurrence in the peritoneum following exposure to peritoneal dialysis fluid. DATA SOURCES: Articles identified through searches on MEDLINE and BIDS and references cited therein. STUDY SELECTION: Studies on the interaction of amino groups with glucose, maltose and glucose polymers. Studies containing evidence of peritoneal advanced glycation end-product formation. DATA EXTRACTION: Studies evaluated as to whether they are in vivo, ex vivo or in vitro under non-physiological or physiological conditions. RESULTS: Protein glycation is slower with maltose and glucose polymers than with equimolar glucose. Advanced glycation end-product formation occurs with all three sugars, but to a greater extent after standard heat sterilization of dialysis fluid and to a lesser extent in heat sterilized fluids containing icodextrin rather than glucose. Glucose degradation products significantly contribute to protein-linked advanced glycation end-product-like fluorescence. Histology and immunohistochemistry demonstrate diabetiform changes and advanced glycation end-products in the peritoneal membrane following exposure to glucose-containing peritoneal dialysis fluids. Their presence is likely to be detrimental to peritoneal function and may contribute to loss of ultrafiltration. CONCLUSIONS: Advanced glycation end-product formation is lower but still significant with heat sterilized peritoneal dialysis fluid containing icodextrin than with glucose. More research is needed to investigate the interaction of glucose degradation products and glucose polymers with proteins and the possible consequences of advanced glycation end-product formation on peritoneal function.

Dialysis Solutions↗
PubMed2000

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

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

Absorption↗
PubMed2000

Ultrafiltration with icodextrins in continuous ambulatory peritoneal dialysis and automated peritoneal dialysis.

Icodextrins (Icos) produce constant linear ultrafiltration (UF). This effect allows Icos to replace glucose during long dwells in continuous ambulatory peritoneal dialysis [CAPD (nighttime)] and automated peritoneal dialysis [APD (daytime)]. However, the effectiveness of Icos in producing UF (IcoUF) is limited by lymphatic reabsorption, whose extent depends partly on posture and physical activity. This paper aims to assess whether the difference in posture and physical activity between daytime dwells in APD and nighttime dwells in CAPD affects IcoUF. Patients undergoing first treatment were retrospectively examined. Ten patients were on CAPD [4 males, 6 females; average age, 73.0 +/- 13.4 years; body surface area (BSA), 1.63 +/- 0.21 m2; total volume per day, 5.6 +/- 1.9 L], and ten were on APD (7 males, 3 females; average age, 67.7 +/- 9.8; BSA, 1.75 +/- 0.22 m2; total volume per night, 10.5 +/- 0.9 L). Ultrafiltration was assessed for seven consecutive days preceding a peritoneal equilibration test (PET) and collection of diuresis. In both groups, 3 patients had no diuresis, and the difference between CAPD and APD was not significant (625 +/- 762 mL vs 780 +/- 878 mL). Moreover, no significant difference was seen in 4-hour dialysate-to-plasma creatinine (D/P) between CAPD (0.65 +/- 0.12) and APD (0.64 +/- 0.05). Dwell times with Icos were shorter in CAPD than in APD (11.5 +/- 1.8 hours vs 14.8 +/- 0.5 hours, p < 0.0005), but the fill volume was not significantly different (1760 +/- 286 mL vs 1790 +/- 249 mL). Water excretion owing to diuresis and dialysis [total water excretion (TWE): 1619 +/- 497 mL CAPD vs 1762 +/- 736 mL APD] and dialytic UF (363 +/- 443 mL CAPD vs 748 +/- 479 mL APD), which is not linked to Icos, were not significantly different between the two groups. The IcoUF and the percentage of IcoUF to TWE were significantly higher in CAPD compared to APD [631 +/- 253 mL (44% +/- 27%) vs 234 +/- 215 mL (19% +/- 19%), p < 0.001 (p < 0.05)]. In conclusion, an upright posture and physical activity seem to produce less IcoUF in APD despite the longer dwell. These factors could, indeed, produce greater intraperitoneal pressure, resulting in increased lymphatic reabsorption during a daytime dwell.

Aged↗
PubMedDate not supplied

The relationship between ultrafiltrate volume with icodextrin and peritoneal transport pattern according to the peritoneal equilibration test.

OBJECTIVE: To establish a relationship between peritoneal transport membrane pattern, analyzed by the peritoneal equilibration test (PET), and drained volume using icodextrin (7.5% Ico) and glucose (3.86% Glu) solutions. DESIGN: Thirty peritoneal dialysis patients were submitted to a standard 4-hour PET and divided into 4 transport categories based on dialysate-to-plasma ratio of creatinine (D/Pcr) and dialysate ratio of glucose at 4 and zero hours of the dwell (D4/D0). Patients were asked to perform exchanges for 2 consecutive nights in 10-hour dwells (2 L 3.86% Glu solution on the first night, and 2 L 7.5% Ico solution on the second night). The drained volume was measured and dialysate samples from the overnight exchanges were obtained for beta2-microglobulin (B2M) levels. RESULTS: PET classification using D/Pcr showed that 46.6% of the patients were high and high-average transporters, or 23.3% when D4/D0 was used. In spite of this difference, both methods showed significant correlation (p = 0.0001, r = 0.862). The mean drained volumes were similar for both solutions (for 3.86% Glu, 2696 +/- 369 mL; for 7.5% Ico, 2654 +/- 424 mL). The high and high-average transport patients classified by D4/D0 achieved a higher ultrafiltration with 7.5% Ico than with 3.86% Glu (p = 0.0235). When classified by D/Pcr, the difference was not significant (p = 0.2243). In the low and low-average transport patients classified by D/Pcr, we observed a significantly lower ultrafiltration when 7.5% Ico was used compared to 3.86% Glu solution (p = 0.0197). Using D4/D0, we saw a tendency toward lower ultrafiltration (p = 0.0719) in the same group. We then correlated the PET results and the difference between drained volume with 7.5% Ico and 3.86% Glu solution [deltaV (I-G)]. We found a significant negative correlation between D4/D0 and deltaV (I-G) (p = 0.002, r = -0.5390), and a positive correlation between D/Pcr and deltaV (I-G) (p = 0.005, r = 0.4932). The levels of B2M obtained with 7.5% Ico were higher than those obtained with 3.86% Glu solution (for 7.5% Ico, 9.47 +/- 6.71 microg/vol; for 3.86% Glu, 7.29 +/- 4.91 microg/vol; p = 0.004). Furthermore, we found significant correlation between the total amount of B2M obtained with 7.5% Ico solution and D4/D0 (p < 0.0001, r = -0.4493), and D/Pcr (p < 0.0001, r = 0.5431). CONCLUSION: Mean drained volume was similar between the two solution groups. High transporters, as defined by D4/D0, achieved higher ultrafiltration with 7.5% Ico than with 3.86% Glu solution. This is most likely due to the higher number of small pores in the peritoneal membrane. Low transporters, as classified by D/Pcr, achieved lower ultrafiltration with 7.5% Ico than with 3.86% Glu solution. The deltaV (I-G) and the PET results showed significant correlation, confirming that high transporters have a higher ultrafiltration volume with 7.5% Ico. The total B2M mass obtained with 7.5% Ico was greater than with 3.86% Glu solution and significantly higher in the high transport patients, indicating a larger number of small pores. Thus, the deltaV (I-G) could give us an idea of the peritoneal transport pattern in peritoneal dialysis patients.

Adult↗
PubMed2002

[Use of icodextrin for diurnal exchange in patients undergoing automatic peritoneal dialysis. Comparison with glucose solutions].

Icodextrin (IC) is an osmotic agent that produces sustained ultrafiltration (UF) during long dwell time periods in peritoneal dialysis patients. The aim of this study was to evaluate the effects of 7.5% IC for the diurnal exchange in automated peritoneal dialysis (APD) patients and to compare them with that of 2.27% glucose solutions. Seventeen patients treated on APD during 13.9 +/- 12.7 months were included. The study was divided into three eight weeks phases. During the baseline period patients used 2.27% glucose for the daytime, second, IC 7.5% was prescribed for the day-exchange, and finally 2.27% glucose solution was used for the last eight weeks. Daytime UF increased in all patients during IC use (-53 +/- 22 to 270 +/- 304 ml/day, p < 0.01). Patients with higher peritoneal permeability capacity obtained more benefits. Daytime urea KT/V and weekly creatinine clearance (WCC) augmented significantly during IC use, but the increase of weekly urea KT/V and WCC was not significant (2.18 +/- 0.45 to 2.26 +/- 0.41 and 62.7 +/- 18 to 66.6 +/- 15 l/week/1.73 m2; respectively). On IC, nightly glucose load significantly decreased (289 +/- 82 to 266 +/- 94 g, p < 0.05), returning to previous value after withdrawal. Plasma osmolality did not change, although plasma sodium levels decreased during IC use (140 +/- 3 to 136 +/- 2, p < 0.001). Serum amylase levels significantly declined during IC use (279 +/- 151 to 29 +/- 9 U/l), returning to previous values after transfer to glucose. Peritoneal function transport parameters and peritoneal protein losses did not change. IC metabolite plasma levels increased during the use of this solution, returning to previous values after withdrawal. In conclusion, IC dialysate is an excellent alternative to glucose dialysate for the day-exchange in APD patients. Daytime UF increased in all patients, but those with higher peritoneal permeability capacity obtained more benefits. The decrease of the glucose peritoneal load overnight and the reduction for more than 50% of exposure time of the peritoneal membrane to glucose solutions, probably make IC solution a more biocompatible fluid.

Adult↗
PubMedDate not supplied

The impact of relapsing sterile icodextrin-associated peritonitis on peritoneal dialysis outcome.

BACKGROUND: The emphasis in peritoneal dialysis (PD) has shifted from a therapy with short-term goals to one of prolonging the life of the peritoneal membrane. Icodextrin (ICO), a starch-derived glucose polymer that is metabolized to maltose, is a valuable osmotic agent in the treatment of PD patients with defective ultrafiltration. However, ICO can cause sterile peritonitis. The manufacturer has recently withdrawn a series of batches of ICO solutions due to evidence of bacterial contamination (a bacterial cell wall breakdown, peptidoglycan). Some cases have been reported of culture-negative ICO-associated peritonitis which relapse on re-challenge. METHODS: We started to use ICO in chronic uremic PD patients in 1997. Ten patients out of 82 treated in our PD unit were exposed to ICO from 1997-2002. We registered 50 peritonitis episodes in this period: 34 were bacterial and 16 culture-negative. Among the 16 episodes of sterile peritonitis, 6 occurred in patients treated with ICO. Four of the 6 ICO treated patients experienced relapsing culture-negative episodes of peritonitis. We reviewed the records of the four patients. RESULTS: The first episodes of sterile ICO-associated peritonitis occurred between February-May 2002. These were clinically very mild and the only sign was abdominal discomfort and a cloudy dialysate containing a number of WBC/mm(3) ranging from 500-800. Cultures were negative. All the ICO solutions were from the batches withdrawn by the manufacturer. ICO (with new batches of solution) was re-introduced in all patients some weeks later to improve ultrafiltration. A new episode of sterile peritonitis occurred with the same characteristics as described above. Three of the four patients were re-challenged with new batches of ICO solution and again sterile peritonitis occurred. One patient was switched directly to hemodialysis (HD); the others were transferred to a program of automated PD including hypertonic glucose solutions. In 8 months all patients were switched to HD because of the failure of ultra-filtration. It is possible that the first episode of sterile peritonitis, associated with the use of an ICO batch suspected of having high peptidoglycan levels could have induced sensitization to ICO, which in turn could have been the cause of the relapse on re-challenge. CONCLUSIONS: The disappointing result of the relapsing culture-negative ICO-associated peritonitis in our patients was the unavoidable switch to HD, due to the inability of the hypertonic glucose solutions to ensure an adequate ultrafiltration. The moral of the story is that the pharmaceutical industry should market products that are more biocompatible and safer for chronic treatments such as PD.

Aged↗
PubMed1997

New principles, better practices, and clearer perceptions in intraperitoneal chemotherapy: clinical experience using icodextrin 20 as a carrier solution.

The rationale for using intraperitoneal chemotherapy is based on three phenomena: certain types of tumor are confined to the abdominal cavity for many years; the ability to deliver the drug directly to the surface of tumor deposits; the pharmacological advantage of attaining high local concentrations of the drug within the cavity. Current techniques of intraperitoneal chemotherapy do not use a specially designed carrier solution, which greatly restricts flexibility and does not permit continuous ambulatory intraperitoneal chemotherapy necessary for optimal use of cell cycle-specific antitumor agents. Using icodextrin 20 as a carrier solution containing 50% of the dose of 5-fluorouracil in a 24-hour dwell, simultaneously with a 24-hour elastomeric infusor device containing 50% of the dose, we have succeeded in carrying out continuous ambulatory intraperitoneal chemotherapy, 5 days out of 7 for up to 12 weeks, exposing the peritoneal contents to drug concentrations a thousand-fold greater than attained in the serum in a Phase I clinical trial. These studies have for the first time demonstrated that it is possible to expose continuously for long periods intraperitoneal tumor deposits to sustained high levels of cell cycle-specific cytotoxic agents.

Antineoplastic Agents↗
PubMed1994

The use of glucose polymer (icodextrin) in peritoneal dialysis: an overview.

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 sustains 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 regimens 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. Although systemic accumulation of glucose polymer breakdown products occurs, it reaches steady-state levels quickly (within 2 weeks) and remains stable throughout the duration of polymer use. In the long-term study these levels of maltose and oligosaccharides over 2.5 years represent the longest exposure of these substances in uremic patients without any clinical or metabolic adverse effects and provides important evidence of its safety. Future work based on ongoing studies suggests 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 and metabolic needs. Icodextrin will be a key component of such solutions.

Dialysis Solutions↗