Effects of New Peritoneal Dialysis Solutions on Leukocyte Recruitment in the Rat Peritoneal Membrane

Abstract

Objectives: Peritonitis remains a principal cause of dropout in peritoneal dialysis (PD). The physiological host response to a peritoneal infection involves a rise in numbers of circulating leukocytes to the peritoneal cavity. We evaluated the effects of (1) conventional peritoneal dialysis fluid (PDF), (2) bicarbonate-based PDF, low in glucose degradation products, and (3) non-glucose PDF on peritoneal leukocyte recruitment in response to an inflammatory stimulus using intravital microscopy. Methods: The visceral peritoneum was exposed to EBSS, conventional lactate-buffered and bicarbonate/lactate-buffered glucose-based PDF and three lactate-buffered non-glucose PDF – icodextrin, amino acid-based PDF and amino acid/glycerol-based PDF. The number of rolling, adhering and extravasated leukocytes and leukocyte rolling velocity was assessed at different time intervals after stimulation with lipopolysaccharide (LPS). Results: Exposure to LPS dissolved in EBSS dramatically increased the number of rolling, adhering and extravasated leukocytes and decreased leukocyte rolling velocity. Conventional PDF completely abolished LPS-induced leukocyte recruitment. Bicarbonate/lactate-buffered PDF only minimally affected the process of leukocyte recruitment, whereas icodextrin PDF resulted in partial inhibition of the immune response. The amino acid-based and the amino acid/glycerol-based PDF inhibited leukocyte recruitment to a similar extent as conventional PDF. Conclusions: Bicarbonate/lactate-buffered PDF has superior biocompatibility towards peritoneal host defense, in spite of its high glucose concentrations. Lactate-buffered non-glucose containing PDF has substantial inhibitory effects on leukocyte recruitment, indicating that the bioincompatibility of high lactate concentrations and/or low pH may not be underestimated.

Influence of Bicarbonate/Low-GDP Peritoneal Dialysis Fluid (Bicavera) on in Vitro and Ex Vivo Epithelial-to-Mesenchymal Transition of Mesothelial Cells

“…The first clinical studies have suggested improved biocompatibility for this solution (12,13). Glucose degradation products promote the transformation of precursors of glycosylation (Amadori products) into advanced glycosylation endproducts (AGEs) (14).…”

Regulation of Experimental Peritonitis: A Complex Orchestration

“…Several peritoneal dialysis solutions, especially lactate-buffered non-glucose containing fluid, could impair leukocytes recruitment, as suggested in lipopolysaccharide (LPS)-induced peritonitis in rats [2]. As stated below, immune responses against offending organisms can adopt different profiles, depending on which kind of bacteria is implicated [3].…”

Solutions for peritoneal dialysis in children: recommendations by the European Pediatric Dialysis Working Group

“…Icodextrin resorption has been studied in only a few children and appears to be faster in infants [73], suggesting a poorer ultrafiltration response compared with adults. The reduced GDP content improves peritoneal host defense mechanisms in an ex vivo model, but not to a similar extent to that of double-chamber PD fluids [54].…”

“…In vitro, multi-chamber PD fluids improve mesothelial cell viability and function, preserve innate peritoneal immune defense mechanisms, and reduce the synthesis and secretion of cytokines related to inflammation, fibrosis, and angiogenesis [46,[50][51][52]. Animal studies confirm improved in vivo peritoneal host defense [53,54], reduced peritoneal TGF-ß and VEGF expression, reduced deposition of AGE, preservation of the mesothelial cell layer, and reduced fibrosis, vasculopathy, and neoangiogenesis [55]. The acute peritoneal hyperperfusion observed with conventional solutions is largely prevented when perfusion is performed with multi-chamber PD fluid [25].…”