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

The in vitro biocompatibility performance of a 25 mmol/L bicarbonate/10 mmol/L lactate-buffered peritoneal dialysis fluid. 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. 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)-1beta-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. 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, human neutrophil viabili