The in vitro biocompatibility performance of a 25mmol/L bicarbonate/10mmol/L lactate-buffered peritoneal dialysis fluid

Abstract

The in vitro biocompatibility performance of a 25 mmol/L bicarbonate/10 mmol/L lactate-buffered peritoneal dialysis fluid.Background. The biocompatibility profile of a new peritoneal dialysis (PD) solution (Physioneal 35) was determined using a selection of in vitro assay systems. Physioneal 35 is buffered by a combination of 25 mmol/L bicarbonate and 10 mmol/L lactate, thereby providing a solution with a total of 35 mmol/L of alkali to complement the currently available 25 mmol/L bicarbonate and 15 mmol/L lactate combination solution, Physioneal 40. In addition, the new solution contains a calcium concentration of 1.75 mmol/L rather than 1.25 mmol/L present in Physioneal 40. Physioneal 35 and 40 are manufactured in double chamber bag systems that permit separation of glucose from the buffer during sterilization. When the two chambers are mixed just before patient use, the resulting solution has a neutral pH and reduced glucose degradation content. Physioneal 35 was evaluated for its cytotoxicity potential using a murine fibroblast assay, its acute effect on human neutrophil and human peritoneal mesothelial cell function, and its in vitro potential to form advanced glycation end products (AGE). The biocompatibility characteristics of this new formulation were compared with that of a conventional, lactate-based solution and to that of its parent formulation, Physioneal 40.Methods. Proliferation of murine fibroblasts was determined after exposure to dialysis fluids for 72 hours. Cell viability was assayed by the ability to take up neutral red dye. Human neutrophils were exposed for 15 minutes to dialysis fluids, and their ATP content and phorbol 12-myristate 13-acetate (PMA) stimulated chemiluminescence response was determined as a measure of viability and respiratory burst activity, respectively. Cellular interleukin (IL)-1b-driven IL-8 synthesis by human mesothelial cells following acute exposure to dialysis fluids was also assessed. Advanced glycation end product formation in the dialysis fluids was measured after 5 and 20 days of incubation with human serum albumin (HSA) as the model protein.Results. In all assays employed, the biocompatibility profile of Physioneal 35 was similar to that of the Physioneal 40 parent formulation. Physioneal 35 showed a significant improvement in biocompatibility performance compared to a pH neutralized conventional lactate-buffered peritoneal dialysis solution in the murine fibroblast assay. In the acute exposure assays,

Glucose-containing peritoneal dialysis fluids regulate leptin secretion from 3T3-L1 adipocytes

“…As a result, cells located in the submesothelial space, e.g. resident fibroblasts and macrophages, have been shown to be activated by solutes from PD fluids [13]. We therefore hypothesized that adipocytes from the omentum, which are in intimate contact with the mesothelial cell layer, also interact with chemical components from PD fluids, especially glucose.…”

Lessons From Single Cell Organisms: Insights Into the Antimicrobial and Toxic Effects of Peritoneal Dialysate Bases

“…Many feel that the majority of toxicity is due to the formation of GDP (79) and, as previously noted, phagocytic activity (16,68–69,80), peritonitis (81), and mesothelial viability (82) appear improved with bicarbonate‐containing low glucose solutions; however, there remains doubt whether the complete elimination of lactate in favor of bicarbonate (83), and glucose (84) in favor of other osmotic agents is desirable. Unfortunately, there may be no advantage in quality of life parameters (85) or peritonitis rates between combined bicarbonate/lactate buffered solutions and standard lactate dialysate in some randomized studies (86).…”

“…Another significant problem to be considered is that of dialysate inhibition of leukocyte function. While it is not totally clear that the effect is due to the carboxylic acids (27,62–67), bicarbonate‐based solutions do have superior neutrophil and macrophage viability (16,68), and, like the toxicity seen in bacteria, the effect also appears related to the ability of organic acids to lower intracellular pH (69).…”

“…To understand why lactate and acetate (and even other salts of other carboxylic acids such as benzoate, citrate, succinate and fumarate, which are now commonly employed to prevent food (13) and catheter infections (14,15)) possess this selective antimicrobial effect, it is important to review the recent developments in our understanding of the biochemical mechanism of the effect. Since there has been a recent emphasis on reduced lactate dialysate to improve biocompatibility (16,17), an improved understanding of the antimicrobial effect might lead to innovative efforts to reduce peritonitis in patients undergoing peritoneal dialysis, and perhaps even some insight into mammalian cell toxicity that could potentially be beneficial in reducing bioincompatibility.…”

Biocompatibility Assessment of Peritoneal Dialysis Solutions With a New In Vitro Model of Preconditioned Human HL60 Cells

“…There are several in vitro models for biocompatibility assessment of PD solutions (7,8). They work with primary isolated cells from blood (9) or from PD effluents, such as macrophages (10), polymorph nuclear cells (11), or peritoneal mesothelial cells (12,13). Permanent cell lines, mostly fibroblastic cells, were used as well, for example, the murine fibroblastic cell line L929 (14).…”