scholarly journals A Novel Formulation of Glucose-Sparing Peritoneal Dialysis Solutions with l-Carnitine Improves Biocompatibility on Human Mesothelial Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 123
Author(s):  
Francesca Piccapane ◽  
Mario Bonomini ◽  
Giuseppe Castellano ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
...  

The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Francesca Piccapane ◽  
Rosa Caroppo ◽  
Arduino Arduini ◽  
Roberto Corciulo ◽  
Roberto Russo ◽  
...  

Abstract Background and Aims The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD). We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD. We previously demonstrated that the water channel AQP1 is expressed in vivo by mesothelial cells. Here, we characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 in mediating water transport during PD and also to test the biocompatibility of glucose-sparing PD solutions (Xylocore), containing xylitol and L-carnitine as the main osmotic agents. Method Cells were grown onto porous cell culture inserts to achieve polarization. Polarization was demonstrated by expression of the tight junction markers Zo-1 and occludin. Transepithelial water transport was measured by TEA+-sensitive microelectrodes. HMC cell monolayers were exposed to PD solutions at the apical side for 8 hours. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT-test, measurement of transepithelial electrical resistance (TEER) and production of pro-inflammatory cytokines by by Luminex xMAP technology. Results HMC cells showed polarized expression of Na+/K+-ATPase and tight junctions markers but no endogenous expression of AQP1. HMC showed a low TEER (40Ω/cm2) compared to renal cells not expressing AQP1(1000Ω/cm2). However, the transepithelial water transport was comparable between the two cell types. Experiments in HMCs transfected with AQP1 cDNA, suggested that the water permeability of HMC was increased by two-fold in the presence of AQP1. Biocompatibility assays indicated that in conventional dialysis solutions glucose concentration decreased cell viability in a dose-dependent manner. Glucose concentration also strongly decreased the TEER, suggesting reduction of the barrier integrity, and increased pro-inflammatory cytokines production. Interestingly, substitution of part of the glucose with xylitol and L-carnitine minimized these effects. Conclusion These results suggest that the mesothelium may represent an additional selective barrier regulating water transport through the water channel AQP1 in PD. Importantly, we also demonstrate that the formulation of glucose-sparing PD solutions containing xylitol and L-carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.


1995 ◽  
Vol 15 (7_suppl) ◽  
pp. 13-23 ◽  
Author(s):  
J. Thomas Hjelle ◽  
Marcia A. Miller-Hjelle ◽  
James W. Dobbie

Substantial derangements of mesothelial biology are observed during experimental simulations of dialysis conditions, inferred from the content of human dialysis effluent and visualized by microscopy of human mesothelial biopsies. Canosmotically active solutions be made biocompatible with the osmoregulatory system of the mesothelium? Can the contributions of the mesothelium to host defenses against inflammation and/or infection be supported during CAPD? Do underlying metabolic derangements present in various kidney diseases and end-stage renal disease, regardless of cause, require customized CAPD protocols and solutions? Use of dialysis solutions less directly toxic to the mesothelium is a necessary step toward some day manipulating peritoneal biology by pharmacological and therapeutic modalities.


1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xueli Lai ◽  
Mingming Nie ◽  
Xiaodong Xu ◽  
Yuanjie Chen ◽  
Zhiyong Guo

Abstract Background Peritoneal dialysis (PD) is a safe and home-based treatment for end-stage renal disease (ESRD) patients. The direct thermal damage of abdominal organs is very rare. Case presentation We report a peritoneal dialysis patient presented abdominal pain and feculent effluent 3 weeks after he instilled hot dialysis solution. In spite of emergency exploratory laparotomy and active treatment, the patient died of septic shock. Biopsy revealed necrosis and perforation of the intestines. Conclusions Delayed bowel perforation by hot fluid is very rare. Standardized performance is of the first importance for peritoneal dialysis patients.


2009 ◽  
Vol 24 (10) ◽  
pp. 2035-2039 ◽  
Author(s):  
Michelle N. Rheault ◽  
Jurat Rajpal ◽  
Blanche Chavers ◽  
Thomas E. Nevins

2019 ◽  
Vol 10 (02) ◽  
pp. 324-326 ◽  
Author(s):  
Ching Soong Khoo ◽  
Tze Yuan Tee ◽  
Hui Jan Tan ◽  
Raymond Azman Ali

ABSTRACTWe report a patient with end-stage renal disease on peritoneal dialysis, who developed encephalopathy after receiving a few doses of cefepime. He recovered clinically and electroencephalographically after having discontinued the culprit agent and undergone hemodialysis. This case highlights the importance of promptly recognizing this reversible encephalopathy, which can lead to the avoidance of unnecessary workup, reduce the length of hospital stay, and thereby improve the patients’ outcome.


2017 ◽  
Vol 37 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Bikaramjit S. Mann ◽  
Braden J. Manns ◽  
Lianne Barnieh ◽  
Matthew J. Oliver ◽  
Daniel Devoe ◽  
...  

The percentage of end-stage renal disease (ESRD) patients treated with peritoneal dialysis (PD) has declined in many countries since the mid-1990s. Barriers to PD have been reviewed extensively in the literature, but evidence about strategies to address these barriers and maximize the safe and effective use of PD is lacking. We therefore decided to conduct a scoping review identifying strategies to maximize PD use in adults with ESRD. Our search strategy included the following online databases: MEDLINE (OVID), EMBASE, PubMed, Cochrane Controlled Trials Register, Current Controlled Trials, and Cochrane Database of Systematic Reviews for articles published from 1974 to November 2013. Experts in the field were contacted for information about other ongoing or unpublished studies. A complementary search was conducted in the gray literature. Websites of national, provincial or regional agencies were searched for documents regarding policies surrounding the use of PD. Individual dialysis centers need to identify barriers to increasing PD in their program and direct targeted strategies to maximize PD utilization. Our review highlights some effective strategies that may be used. Our review also highlights the need for further research into strategies to maximize PD utilization.


2017 ◽  
Vol 37 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Charlotte E. Grantham ◽  
Katherine L. Hull ◽  
Matthew P.M. Graham-Brown ◽  
Daniel S. March ◽  
James O. Burton

Cardiovascular mortality in the end-stage renal disease (ESRD) population remains the leading cause of death. Targeting traditional cardiovascular risk factors has proven unsuccessful in this patient population, and therefore attention has turned to risk factors related to chronic kidney disease (CKD). The toxicity of high-glucose peritoneal dialysis (PD) solutions has been well documented. The breakdown of glucose into glucose degradation products (GDP) and advanced glycation end-products (AGE) has the ability to alter cell viability and cause premature apoptosis and is strongly correlated with interstitial fibrosis and microvascular sclerosis. Biocompatible solutions have been introduced to combat the hostile milieu to which PD patients are exposed.Given the considerable cardiovascular burden for PD patients, little is known about the cardiovascular impact the new biocompatible solutions may have. This review analyzes the existing literature regarding the mechanisms through which low-GDP solutions may modulate cardiovascular risk. Interventions using low-GDP solutions have provided encouraging changes in structural cardiovascular measures such as left ventricular mass (LVM), although metabolic changes from reduced GDP and AGE exposure yield inconclusive results on vascular remodelling. It is thought that the local effects of reduced glucose exposure may improve membrane integrity and therefore fluid status. Further research in the form of a robust randomized controlled trial should be carried out to assess the true extent of the cardiovascular benefits these biocompatible solutions may hold.


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