-
Drugs 2003Icodextrin (Extraneal) is a high molecular weight glucose polymer developed specifically for use as an alternative osmotic agent to dextrose during the once-daily... (Review)
Review
UNLABELLED
Icodextrin (Extraneal) is a high molecular weight glucose polymer developed specifically for use as an alternative osmotic agent to dextrose during the once-daily long-dwell exchange in peritoneal dialysis (PD). Isosmotic 7.5% icodextrin solution induces transcapillary ultrafiltration (UF) by a mechanism resembling 'colloid' osmosis (unlike hyper-osmolar dextrose-based solutions, which induce UF by crystalline osmosis). In addition, absorption of icodextrin from the peritoneal cavity is relatively slow compared with that of dextrose; this results not only in UF of longer duration, but also a lower carbohydrate load compared with medium (2.5%) and strong (4.25%) dextrose exchanges. In randomised clinical trials of up to 2 years in duration, administration of icodextrin for the long (8- to 16-hour) overnight exchange in continuous ambulatory peritoneal dialysis (CAPD) or daytime exchange in automated peritoneal dialysis (APD) produced net UF which exceeded that with 1.5% and 2.5% dextrose solutions (thereby improving fluid balance), and was equivalent to that with 4.25% dextrose solution. Icodextrin also increased peritoneal clearances of creatinine and urea nitrogen compared with 2.5% dextrose solution. The increase in UF volume with icodextrin was enhanced in CAPD patients with high peritoneal membrane permeability (i.e. high and high-average transporters), maintained in the small number of patients followed-up for 2 years and sustained during episodes of peritonitis. Icodextrin reduced the percentage of patients with net negative UF in contrast to 1.5% and 2.5% dextrose and, in noncomparative studies, extended PD technique survival in patients who had failed dextrose-based dialysis. The use of icodextrin was also associated with some symptomatic improvements and health-related quality of life advantages, and no adverse effect on patient survival, compared with dextrose, although confirmation of these findings is ideally required in appropriately designed studies. The tolerability of icodextrin was generally similar to that of dextrose-based solutions in controlled clinical trials, although there was an approximate three-fold increase in the risk of new skin rash (5.5% vs 1.7%). However, reports of severe cutaneous hypersensitivity reactions remain rare; this possibility should not preclude the use of the polymer.
CONCLUSION
7.5% icodextrin solution offers the first feasible alternative to conventional dextrose solutions for the once-daily long-dwell exchange in PD. It is effective, generally well tolerated and appears to be most useful in situations of reduced or inadequate UF with dextrose, including in high and high-average transporters, during episodes of peritonitis and patients who have failed dextrose-based dialysis.
Topics: Clinical Trials as Topic; Dialysis Solutions; Drug Interactions; Glucans; Glucose; Humans; Icodextrin; Kidney Failure, Chronic; Peritoneal Dialysis; Quality of Life
PubMed: 12962523
DOI: 10.2165/00003495-200363190-00011 -
Peritoneal Dialysis International :... 1994To determine if microwave heating of dialysis solutions to 37 degrees C produced focal overheating (hot spots) and caramelization of dextrose.
OBJECTIVE
To determine if microwave heating of dialysis solutions to 37 degrees C produced focal overheating (hot spots) and caramelization of dextrose.
DESIGN
In vitro determination of conditions for controlling time, temperature, and procedures. Bags had been stored at ambient room temperature.
MAIN OUTCOME MEASURES
Solution and external bag surface temperature determinations. Dextrose degradation products determined spectrophotometrically. Microscopy for potential caramel precipitates.
RESULTS
A microwave oven with no rotation tray produced uneven heating of bags of two commercially available concentrations of dialysis solutions. The greatest hot spots were evident in spike ports. External bag surface temperatures were within 0.20 degrees C of reservoir temperatures. Initial solution temperatures correlated with temperatures of the solutions after microwave heating (r = 0.895). No statistically significant differences were found between dextrose degradation product concentrations of unheated and heated solutions, including hot spots. No precipitates were observed microscopically.
CONCLUSIONS
Despite the presence of solution hot spots in bag infusion ports, 37 degrees C temperatures were achievable in the bag reservoirs with no evidence of increased glucose degradation. This outcome is assured if the initial temperature and the microwave conditions (procedure, time, mixing of solution) are held constant, and the external bag temperatures are measured after heating.
Topics: Dialysis Solutions; Glucose; Hot Temperature; Humans; Microwaves; Peritoneal Dialysis
PubMed: 8043671
DOI: No ID Found -
Translational Research : the Journal of... May 2009Long-term peritoneal dialysis induces morphological changes that may lead to gradual functional impairment of the peritoneal membrane. These changes are characterized by...
Long-term peritoneal dialysis induces morphological changes that may lead to gradual functional impairment of the peritoneal membrane. These changes are characterized by progressive reduction in solute transport or ultrafiltration failure. The mechanism of the peritoneal response to dialysis fluids has not yet been fully elucidated. We used video-microscopy for in vivo evaluation of microhemodynamics and peritoneal microvascular inflammatory response, after a single intraperitoneal exposure of rats to commercial PD fluids: (1) glucose 1.5 % PD solution; (2) lactate buffered glucose 4.25% PD solution; (3) Icodextrin 7%; (4) bicarbonate buffered glucose 3.86% PD fluid; and 5) Hanks solution. Sham-control groups were not injected. A 5-h exposure of the peritoneal membrane to glucose 1.5% PD solution or to Hanks solution did not induce a significant change in leukocyte rolling and adhesion. In contrast, PD solutions containing glucose 4.25% or Icodextrin 7.5% caused a significant 2-3-fold increase in leukocyte rolling (P < 0.001) and adhesion (P < 0.001) and a significant increase in venular blood flow velocity (P < 0.01) and shear rates (P < 0.05 for glucose 4.25%, and P < 0.01 for Icodextrin). Exposure to glucose 3.86% bicarbonate buffered (Physioneal) solution was associated with the lowest values of leukocyte rolling and adhesion among the PD solutions and with extremely higher venular flow velocities and shear rates. A single exposure to conventional PD solutions with a high concentration of glucose (4.25%) or polyglucose (Icodextrin 7.5%) induces changes consistent with an early peritoneal inflammatory response that may be attenuated by the use of bicarbonate-based fluids.
Topics: Animals; Dialysis Solutions; Male; Peritoneal Dialysis; Peritoneum; Random Allocation; Rats; Rats, Sprague-Dawley; Splanchnic Circulation
PubMed: 19375686
DOI: 10.1016/j.trsl.2009.01.006 -
Peritoneal Dialysis International :... 2005Peritoneal dialysis (PD) solutions using glucose as osmotic agent have been used for more than two decades as effective treatment for patients with end-stage renal... (Review)
Review
Peritoneal dialysis (PD) solutions using glucose as osmotic agent have been used for more than two decades as effective treatment for patients with end-stage renal disease. Although alternative osmotic agents such as amino acids and macromolecular solutions, including polypeptides and glucose polymers, are now available, glucose is still the most widely used osmotic agent in PD. It has been shown to be safe, effective, readily metabolized, and inexpensive. On the other hand, it is widely assumed that exposure of the peritoneal membrane to high glucose concentrations contributes to both structural and functional changes in the dialyzed peritoneal membrane. As in diabetes, glucose, either directly or indirectly through the generation of glucose degradation products or the formation of advanced glycation end products, may contribute to peritoneal membrane failure. Although efforts to reduce glucose toxicity have been made for years, only a few suggestions, such as dual-bag systems with bicarbonate as buffer system, have found broader acceptance. Recently, some interesting new approaches to the problem of glucose-related toxicity have been made, but further investigations will be necessary before they can be used clinically. This review will focus on adverse effects of glucose in PD solutions and summarize different aspects of glucotoxicity and potential therapeutic interventions.
Topics: Dialysis Solutions; Glucose; Glycation End Products, Advanced; Humans; Inactivation, Metabolic; Osmosis; Peritoneal Dialysis; Peritoneum
PubMed: 16178471
DOI: No ID Found -
Therapeutic Apheresis and Dialysis :... Dec 2023Hemodialysis is considered a treatment of choice for patients with renal failure worldwide, allowing the replacement of some kidney functions by diffusion and... (Review)
Review
Hemodialysis is considered a treatment of choice for patients with renal failure worldwide, allowing the replacement of some kidney functions by diffusion and ultrafiltration processes. Over 4 million people require some form of renal replacement therapy, with hemodialysis being the most common. During the procedure, contaminants in the water and the resulting dialysate may pass into the patient's blood and lead to toxicity. Thus, the quality of the associated dialysis solutions is a critical issue. Accordingly, the discussion of the importance of a dialysis water delivery system controlled by current standards and recommendations, with efficient monitoring methods, disinfection systems, and chemical and microbiological analysis, is crucial for improving the health outcomes of these patients. The importance of treatment, monitoring, and regulation is emphasized by presenting several case studies concerning the contamination of hemodialysis water and the adverse effects on the respective patients.
Topics: Humans; Water Quality; Renal Dialysis; Dialysis Solutions; Ultrafiltration; Continuous Renal Replacement Therapy; Hemodialysis Solutions
PubMed: 37381091
DOI: 10.1111/1744-9987.14032 -
Nephrology, Dialysis, Transplantation :... Dec 2005
Topics: Dialysis Solutions; Europe; Humans; Peritoneal Dialysis
PubMed: 16263745
DOI: 10.1093/ndt/gfi1119 -
Peritoneal Dialysis International :... 2008Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components...
BACKGROUND
Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.
METHODS
Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution.
RESULTS
All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H(+) concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA).
CONCLUSIONS
(1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H(+)]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H(+)], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.
Topics: Animals; Biological Transport; Buffers; Dialysis Solutions; Glucans; Glucose; Icodextrin; Lactates; Male; Microcirculation; Osmolar Concentration; Peritoneal Cavity; Peritoneal Dialysis; Peritoneum; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Regional Blood Flow; Vasodilation
PubMed: 18474922
DOI: No ID Found -
Seminars in Dialysis 2004To prevent pyrogenic reactions during hemodialysis, it is recommended that bacteria and endotoxin in dialysate not exceed 100-200 colony forming units (CFU)/ml and... (Review)
Review
To prevent pyrogenic reactions during hemodialysis, it is recommended that bacteria and endotoxin in dialysate not exceed 100-200 colony forming units (CFU)/ml and 0.25-2 endotoxin units (EU)/ml, respectively. While these limits are adequate to prevent acute pyrogenic reactions, data are accumulating to suggest they may not prevent stimulation of chronic inflammation in hemodialysis patients. Fragments of endotoxin and other bacterial products capable of stimulating immune cells cross low-flux and high-flux membranes in vitro. In clinical studies, use of ultrapure dialysate (bacteria < 0.1 CFU/ml and endotoxin < 0.03 EU/ml) is associated with lower concentrations of inflammatory markers and acute phase reactants than are observed with dialysate meeting current quality recommendations. Moreover, observational studies suggest a link between clinical outcomes and dialysate purity. Treatment of patients with ultrapure dialysate is reported to improve nutritional status, increase responsiveness to erythropoietin, slow the decline in residual renal function, lessen cardiovascular morbidity, and decrease the incidence of beta(2)-microglobulin amyloidosis. To date, however, none of these studies has shown a cause-and-effect relationship between dialysate purity and outcome. Further, there are no data defining the concentration dependence of outcomes on dialysate purity and the relative importance of dialysate purity as a trigger of inflammation remains unclear. While the technology exists to routinely provide ultrapure dialysate, controlled clinical trials are still needed to answer the question of whether or not introducing ultrapure dialysate into routine clinical practice represents an efficient use of limited resources in terms of decreasing inflammation and improving outcomes in hemodialysis patients.
Topics: Bacteria; Biomarkers; Dialysis Solutions; Fever; Humans; Inflammation; Kidney Failure, Chronic; Renal Dialysis; Sepsis; Water Purification
PubMed: 15660580
DOI: 10.1111/j.0894-0959.2004.17617.x -
Seminars in Dialysis 2001Automated peritoneal dialysis (APD) is the fastest growing technique of peritoneal dialysis. However, recently APD has displayed some limitations imposed by the... (Review)
Review
Automated peritoneal dialysis (APD) is the fastest growing technique of peritoneal dialysis. However, recently APD has displayed some limitations imposed by the characteristics of the technique and by the characteristics of the peritoneal membrane of some patients. In general, the advent of a new technique such as continuous flow peritoneal dialysis (CFPD) should be seen as a benefit for several patients based on different considerations: CFPD is a high-efficiency technique which could overcome some of the limitations imposed by other techniques in terms of adequacy targets and performance. CFPD may become a useful tool to keep patients on PD who would otherwise be transferred to hemodialysis. CFPD may present advantages in terms of biocompatibility and also in terms of the possible modulation of the peritoneal solution to patient needs. Recent developments in technology seem to have made CFPD easily feasible and well tolerated. A new era of PD is probably beginning and CFPD will definitely represent one of the key issues in the future of PD.
Topics: Catheterization; Dialysis Solutions; Humans; Peritoneal Dialysis
PubMed: 11679112
DOI: 10.1046/j.1525-139x.2001.00095.x -
Current Opinion in Nephrology and... Mar 2014This review will examine the impact of neutral pH, low glucose degradation product (GDP) peritoneal dialysis fluid use on patient-level clinical outcomes in peritoneal... (Review)
Review
PURPOSE OF REVIEW
This review will examine the impact of neutral pH, low glucose degradation product (GDP) peritoneal dialysis fluid use on patient-level clinical outcomes in peritoneal dialysis patients.
RECENT FINDINGS
Recently published results from the balANZ trial and a meta-analysis suggest that the use of neutral pH, low GDP peritoneal dialysis fluids leads to better preservation of residual renal function, including residual diuresis, without added harmful effects. The impact of neutral pH, low GDP peritoneal dialysis fluids on other clinical outcomes (e.g. peritonitis) remains uncertain due to conflicting results from randomized controlled trials. A meta-analysis was unable to clarify this further due to generally suboptimal trial quality and insufficient statistical power.
SUMMARY
At present, based on the best available evidence, the use of neutral pH, low GDP peritoneal dialysis fluids is associated with some important clinical benefits without added harm. Further studies in the area are needed to establish the cost-effectiveness of this therapy and to clarify the effects of biocompatible fluids on patient-level outcomes, such as peritonitis, quality of life, technique survival and patient survival.
Topics: Animals; Blood Glucose; Dialysis Solutions; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Diseases; Peritoneal Dialysis; Treatment Outcome
PubMed: 24378773
DOI: 10.1097/01.mnh.0000441046.13912.1f