Prevention of Peritoneal Sclerosis: A New Proposal to Substitute Glucose with Carnitine Dialysis Solution (Biocompatibility Testing in Vitro and in Rabbits)

2005 ◽  
Vol 28 (2) ◽  
pp. 177-187 ◽  
Author(s):  
E. Gaggiotti ◽  
A. Arduini ◽  
M. Bonomini ◽  
G. Valentini ◽  
G. Sacchi ◽  
...  

Aim Commercial glucose peritoneal dialysis solutions expose the peritoneum to hyperosmolar glucose containing variable amounts of non-enzymic breakdown products of glucose. These solutions are toxic for the peritoneum. The aim of the present study is to compare in vitro and in vivo characteristics of a new dialysis solution containing carnitine, a naturally occurring compound, as substitute of glucose. Material and Methods We compared in vitro and in the rabbit a new peritoneal dialysis solution containing carnitine, with two standard bicarbonate glucose peritoneal dialysis solutions and a solution containing icodextrin. Results In vitro and in vivo the solution containing carnitine seems to be more biocompatible than standard glucose solutions and those containing icodextrin. Conclusions In our study the peritoneal dialysis solution containing carnitine seems to prevent the mesothelial changes observed with solutions containing glucose. Since carnitine has been extensively studied and seems to be well tolerated by hemodialysis patients, even at high doses for long periods, clinical trials in humans may be planned in the near future.

2003 ◽  
Vol 23 (2) ◽  
pp. 123-126 ◽  
Author(s):  
◽  
Marina Penélope Catalan ◽  
Jaime Esteban ◽  
Dolores Subirá ◽  
Jesús Egido ◽  
...  

Background Inhibition of caspases improves the antibacterial capacity of leukocytes cultured with peritoneal dialysis solutions, and improves the prognosis of septic, polymicrobial experimental peritonitis. Objective To test whether inhibition of caspases alters the evolution of peritonitis in the presence of peritoneal dialysis solution. Design 32 mice were assigned to therapy with either the pan-caspase inhibitor zVAD or vehicle for 48 hours following infection with Staphylococcus aureus, in the presence of lactate-buffered, 4.25% glucose peritoneal dialysis solution. 16 mice received vehicle in phosphate-buffered saline. Main Outcome Measure Number of bacteria recovered from the peritoneum at 48 hours. Results Peritoneal dialysis solution accelerated leukocyte apoptosis. zVAD decreased the number of apoptotic peritoneal leukocytes and the number of bacteria recovered from the peritoneum at 48 hours (zVAD 2.8 ± 0.3 vs vehicle 3.9 ± 0.2 log colony forming units of S. aureus, p = 0.007). Conclusions Inhibition of caspases accelerates peritoneal bacterial clearance in the presence of peritoneal dialysis solutions in vivo in the experimental setting. Inhibition of caspases should be explored as a mean to accelerate recovery following peritonitis in the clinical setting.


1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 95-97 ◽  
Author(s):  
John Williamson Balfe ◽  
Izhar Qamar

Changes in the formulation of peritoneal dialysis solutions will continue. For the present, dextrose dialysis will remain the osmotic solute of choice. How amino acids and glucose polymers as solute replace ments for glucose fit into the dialysis prescription remains to be seen. The lower concentration of calcium and magnesium appears to be gaining acceptance in many centers. It is feasible that in the next few years the challenge of adding bicarbonate to the peritoneal dialysis solution will be circumvented, because there appears to be a real clinical need for such an improvement. Pediatric modifications will be necessary, appreciating that such changes will have an economic penalty, and thus must have proven value.


2002 ◽  
Vol 22 (5) ◽  
pp. 593-601 ◽  
Author(s):  
El Rasheid Zakaria ◽  
David A. Spain ◽  
Patrick D. Harris ◽  
R. Neal Garrison

Objectives Conventional peritoneal dialysis solutions are vasoactive. This vasoactivity is attributed to hyperosmolality and lactate buffer system. This study was conducted to determine if the vasodilator property of commercial peritoneal dialysis solutions is a global phenomenon across microvascular levels, or if this vasodilation property is localized to certain vessel types in the small intestine. Design Experimental study in a standard laboratory facility. Interventions Hemodynamics of anesthetized rats were monitored while the terminal ileum was prepared for in vivo intravital microscopy. Vascular reactivity of inflow arterioles (A1), branching (A2), and arcade, as well as pre-mucosal (A3) arterioles was assessed after suffusion of the terminal ileum with a non-vasoactive solution or a commercial 4.25% glucose-based solution (Delflex; Fresenius USA, Ogden, Utah, USA). Vascular reactivity of three different level venules was also assessed. Maximum dilation response was obtained from sequential applications of the endothelial-dependent dilator, acetylcholine (10–5 mol/L), and the endothelial-independent nitric oxide donor, sodium nitroprusside (NTP; 10–4mol/L). Results Delflex induced an instant and sustained vasodilation that averaged 28.2% ± 2.4% of baseline diameter in five different-level arterioles, ranging in size between 7 μ and 100 μ. No significant vascular reactivity was observed in three different-level venules. Delflex increased intestinal A1 blood flow from baseline 568 ± 31 nL/second to 1049 ± 46 nL/sec ( F = 24.7, p < 0.001). Similarly, intestinal venous outflow increased to 435 ± 17 nL/sec from a baseline outflow of 253 ± 59 nL/sec ( F = 4.7, p < 0.05). Adjustment of the initial pH of Delflex from 5.5 to 7.4 resulted in similar microvascular responses before pH adjustment. Conclusions Ex vivo exposure of intestinal arterioles to conventional peritoneal dialysis solutions produces a sustained and generalized vasodilation. This vasoactivity is independent of arteriolar level and the pH of the solution. Dialysis solution-mediated vasodilation is associated with doubling of A1 intestinal arteriolar blood flow. Addition of NTP at an apparent clinical dose does not appear to produce any further significant arteriolar dilation than that induced by dialysis solution alone. Experimental data that estimate the exchange vessel surface area per unit volume of tissue will be required to make a correlation with permeability in order to extrapolate our findings to clinical in vivo conditions.


1994 ◽  
Vol 17 (4) ◽  
pp. 191-194 ◽  
Author(s):  
T.S. Ing ◽  
A.W. Yu ◽  
P.V. Podila ◽  
F.Q. Zhou ◽  
E.W. Kun ◽  
...  

Exposure of human neutrophils to conventional, acidic, lactate-based peritoneal dialysis solutions for 5 minutes results in a depression of superoxide generation. In spite of restoration of extracellular pH to 7.4, these stunned cells failed to recover their ability to generate the anion after a period of an hour.


1986 ◽  
Vol 9 (6) ◽  
pp. 387-390 ◽  
Author(s):  
R. Khanna ◽  
Z. J. Twardowski ◽  
D.G. Oreopoulos

Glucose has more advantages than drawbacks and is now the sole agent used in clinical practice. Yet there is interest in finding a substitute for glucose as an osmotic agent in peritoneal dialysis solution. Work has identified several promising agents such as albumin, amino acids, gelatin and glycerol but it appears that every one of them, including glucose, would be useful for a short-dwell or for a long-dwell exchange but not for both. Some of them, such as albumin and the amino acids, are close to being an ideal osmotic agent but are prohibitively costly to manufacture. We predict that interest in the future will focus on dialysis solutions containing a mixture of osmotic agents. Such a solution would be acceptable for both short and long-dwell exchanges. It will have a sufficiently low concentration of different agents to minimize toxicity and long-term undesirable side effects. We expect that solutions will be available to better meet patients needs in the near future.


1986 ◽  
Vol 20 (9) ◽  
pp. 697-700 ◽  
Author(s):  
Paul C. Walker ◽  
Ralph E. Kaufmann ◽  
Neil Massoud

The compatibility of cefazolin and gentamicin in fluid commonly used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Five admixtures containing cefazolin (75 mg/L and 150 mg/L) and gentamicin (8 mg/L), alone and in combination, were prepared in 1.5% dextrose peritoneal dialysis solution. Solutions were stored for 48 hours at 4°C, 26°C, and 37°C; aliquots for drug assay were obained at 0, 4, 8, 24, and 48 hours. HPLC and immunofluorescent assays were used to determine cefazolin and gentamicin concentrations, respectively. The cefazolin and gentamicin concentration changes over the study period did not reach statistical significance. Maximal cefazolin and gentamicin losses (12 and 7 percent of the initial concentrations, respectively) were observed at 48 hours in solutions stored at 37°C. No significant differences in concentration changes were observed between combination solutions and solutions containing either cefazolin or gentamicin alone. Cefazolin and gentamicin, alone or in combination, are compatible for at least 48 hours in CAPD solutions.


1992 ◽  
Vol 15 (11) ◽  
pp. 661-665 ◽  
Author(s):  
A.W. Yu ◽  
X.J. Zhou ◽  
F.Q. Zhou ◽  
Z.M. Nawab ◽  
V.C. Gandhi ◽  
...  

Exposure of human neutrophils to a conventional, acidic, lactate-containing peritoneal dialysis solution (PDS) resulted in the development of a prompt and substantial intracellular acidosis. It is possible that this intracellular acidosis contributes to cellular dysfunction.


1997 ◽  
Vol 20 (12) ◽  
pp. 673-677 ◽  
Author(s):  
K. Wieczorowska-Tobis ◽  
K. Korybalska ◽  
A. Polubinska ◽  
M. Radkowski ◽  
A. Breborowicz ◽  
...  

This study was designed to analyze the complex morphologic and functional effects of dialysis solutions on peritoneum in a rat model on chronic peritoneal dialysis. Peritoneal catheters were inserted into 10 male, Wistar rats and the animals were dialyzed twice daily for 4 weeks with 4.25% Dianeal. During the study we observed two opposite effects: healing of the peritoneum after catheter implantation - decreased cell count in dialysate, decreased permeability of the peritoneum to glucose and total protein, increased volume of drained dialysate; and damage to the membrane due to its exposure to peritoneal dialysis solution - increased hyaluronic acid levels in dialysate, a tendency of the peritoneum to thicken when compared to non-dialyzed animals. Our rat model of CAPD may be used for quantitative and qualitative assessment of the effects of peritoneal dialysis solution on the peritoneum during chronic dialysis


2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 5-9 ◽  
Author(s):  
C.J. Holmes

Pre-clinical biocompatibility testing of peritoneal dialysis (PD) solutions has become an integral part of new solution development. The construction of a pre-clinical screening program for solution biocompatibility should take a hierarchical approach, starting with in vitro cell viability and function assays. The selection of cell types and assay systems for the in vitro studies should be broad enough to permit a balanced interpretation. Whenever possible, animal models are recommended for the next hierarchical level of testing, followed by human ex vivo study designs. Designs of the latter sort provide evidence that a new solution formulation is exerting an altered biological response in vivo; the response is not purely an in vitro artifact or restricted to a given animal species. This article discusses the various approaches available for biocompatibility testing during the pre-clinical phase of solution development, with an emphasis on the advantages and drawbacks of each method.


1989 ◽  
Vol 9 (4) ◽  
pp. 325-328 ◽  
Author(s):  
Leo Martis ◽  
Kenneth D. Serkes ◽  
Karl D. Nolph

The widespread use of calcium carbonate as a phosphate binder is limited by its tendency to develop hypercalcemia in some patients using effective dosages needed to control hyperphosphatemia. Most common continuous ambulatory peritoneal dialysis (CAPD) regimens using dialysis solutions containing 3.5 mEqlL of calcium result in net absorption of calcium from the dialysis solution and, hence limit the amount of oral calcium that can be administered. Peritoneal dialysis solutions with reduced calcium levels are needed for effective use of CaCO3 to control hyperphosphatemia in some dialysis patients.


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