Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions.

Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of PM integrity and transport function is the key to the success of PD therapy, particularly in the long term, since the prolonged exposure to unphysiological hypertonic glucose-based PD solutions in current use is detrimental to the PM, with progressive loss of peritoneal ultrafiltration capacity causing technique failure. Moreover, absorbing too much glucose intraperitoneally from the dialysate may give rise to a number of systemic metabolic effects. Here we report the preliminary results of the first clinical experience based on the use in continuous ambulatory PD (CAPD) patients of novel PD solutions obtained through partly replacing the glucose load with other osmotically active metabolites, such as L-carnitine and xylitol. Ten CAPD patients were treated for four weeks with the new solutions. There was good tolerance to the experimental PD solutions, and no adverse safety signals were observed. Parameters of dialysis efficiency including creatinine clearance and urea Kt/V proved to be stable as well as fluid status, diuresis, and total peritoneal ultrafiltration. The promising tolerance and local/systemic advantages of using L-carnitine and xylitol in the PD solution merit further research.

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.

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.

Hyperglycaemia harms vascular health and promotes platelet aggregation. Reducing glucose concentration is crucial, and sugar alcohols may aid this effort. Used for over 50 years in food, cosmetic, and pharmaceutical industries, erythritol and xylitol minimally affect plasma glucose and insulin levels while promoting the release of beneficial gastrointestinal hormones such as e.g. glucagon-like peptide-1. These properties make them particularly appealing for individuals with diabetes, obesity, and metabolic syndrome. Recent pilot trials suggest that xylitol and erythritol might temporarily alter platelet aggregation. Studies on critically ill patients receiving large intravenous doses and Mendelian randomisation trials do not link sugar alcohols to significant cardiovascular risks. Sugar alcohols are also endogenously produced in the body, and while their increased production under certain conditions is not fully understood, it requires further research. This review discusses the physiology and metabolism of erythritol and xylitol, and other sugar alcohols, their roles in metabolomic profiling, effects on platelet aggregation and cardiovascular risk, related genetic disorders, vascular impacts, and usage in critically ill patients.