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

Piccapane, Francesca; Bonomini, Mario; Castellano, Giuseppe; Gerbino, Andrea; Carmosino, Monica; Svelto, María; Arduini, Arduino; Procino, Giuseppe

doi:10.3390/ijms22010123

Cited by 13 publications

(18 citation statements)

References 63 publications

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“…Glucose has been partially replaced by two osmometabolic agents, xylitol and L-carnitine. Treatment with this new formulation resulted a higher cell viability, better preservation of the integrity of the mesothelial layer, and reduced release of proinflammatory cytokines, as reported in a recent in vitro study (70).…”

Section: Bioincompatibility Of Pd Solutionssupporting

confidence: 79%

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

et al. 2021

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Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the peritoneal membrane. This process may be caused by a number of insults including pathological conditions linked to clinical practice, such as peritoneal dialysis, abdominal surgery, hemoperitoneum, and infectious peritonitis. All these events may cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy. Among the cellular processes implicated in these peritoneal alterations is the generation of myofibroblasts from mesothelial cells and other cellular sources that are central in the induction of fibrosis and in the subsequent functional deterioration of the peritoneal membrane. Myofibroblast generation and activity is actually integrated in a complex network of extracellular signals generated by the various cellular types, including leukocytes, stably residing or recirculating along the peritoneal membrane. Here, the main extracellular factors and the cellular players are described with emphasis on the cross-talk between immune system and cells of the peritoneal stroma. The understanding of cellular and molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.

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Section: Bioincompatibility Of Pd Solutionssupporting

confidence: 79%

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

et al. 2021

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“…The formulation of the novel PD solution (XyloCore) includes a low glucose amount (27.7 mmol/L), that did not seem to have the deleterious effects the higher concentration did [ 35 ], in order to take advantage of its UF ability. In a recent study [ 38 ], we compared the effects on mesothelial cells exposed only at the apical side (thus mimicking the condition of a PD dwell) of several different PD solutions including standard glucose-based, neutral ph low GDP (Physioneal, Bicavera), icodextrin, and amino acids [ 38 ]. Findings of the study 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 by the novel PD solution [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Once inside the cell, D-Xylitol is oxidized to D-xylulose and then phosphorylated to D-xylulose-5-phosphate, an intermediate of the pentose monophosphate shunt [ 31 ]. Xylitol can act as an osmotic agent [ 37 ], improves insulin sensitivity and glycemic control in diabetic patients [ 31 , 37 ], and has a good biocompatibility and toxicity profile [ 32 , 38 ]. In Germany, xylitol is approved for parenteral nutrition.…”

Section: Introductionmentioning

confidence: 99%

Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

et al. 2021

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Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

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“…We recently tested the biocompatibility of the new experimental PD solution by recreating in vitro a mesothelium-like structure, exploiting a cell line of human mesothelium grown to confluence on porous cell culture inserts previously coated with a layer of an extracellular matrix [ 147 ]. Using this experimental model, we compared the effects induced by several conventional glucose-based PD solutions, glucose-free solutions, and the novel dialysate formulation with xylitol and L-carnitine.…”

Section: Strategies Devised To Improve the Biocompatibility Of Pd Solutionmentioning

confidence: 99%

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)

Bonomini

Masola

Procino

et al. 2021

IJMS

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Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling—and their metabolic sequelae—on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.

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

Cited by 13 publications

References 63 publications

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)

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