Effect of Different Buffers on the Biocompatibility of Capd Solutions

Abstract

Commercially available solutions for continuous ambulatory peritoneal dialysis (CAPO) affect the viability and function of the cells in the peritoneal cavity. The low biocompatibility of the solutions may be caused by a low pH, hyperosmolality, high glucose content, and lack of potassium, glutamine, and other components essential for normal cellular functions. The nature of the buffer employed is also important for the cytotoxicity of the solutions. Lactate, the most frequently used buffer, has been shown to inhibit cellular functions important for the peritoneal defense system including phagocytosis, bacterial killing, and secretion of cytokines. It is generally believed that the cytotoxicity of lactate is caused by lowering of intracellular pH and impairment of metabolism due to changed redox potentials. However, the cytotoxicity of lactate is highly dependent upon the pH of the solutions, indicating that passive or active diffusion across the cell membrane is determining the effects of lactate. Bicarbonate has been heavily advocated as an alternative buffer because it is the most important naturally occurring buffer in plasma and it enables a pH of approximately 7.4 in the solutions. However, due to sedimentation of calcium carbonate (CaCO3) and production of toxic glucose metabolites it is difficult to prepare and store bicarbonate-based solutions. Moreover, investigations have revealed that even bicarbonate-based solutions are not optimal regarding biocompatibility, presumably due to a paradoxical intracellular acidification caused by influx of carbon dioxide (CO2). More recently, the effect of other buffers such as pyruvate and histidine have been examined. Especially pyruvate is a promising new buffer candidate.

Conventional CAPD solutions based on lactate have been shown to impair a wide variety of cell functions important for the peritoneal host defense. Apart from the influence of hyperosmolality, high glucose concentration, lack of potassium, glutamine, and other factors, this seems to be due to the combination of low pH and high lactate concentration. Presumably, lactate carries protons across the membrane, which results in intracellular acidification and increased intracellular lactate concentration, both of which may impair cell metabolism and function.

Bicarbonate-based solutions are less toxic than lactate-based solutions -primarily attributable to the higher pH. However, experiments performed by our group have indicated that bicarbonate concentrations that are too high may also affect cell function, and that a solution containing both bicarbonate and lactate may be superior. However, further studies are needed to fully elucidate this problem.

Pyruvate seems to be a promising new buffer candidate with lower toxicity than lactate solutions at identical pH and glucose content. Comparison of pyruvate, lactate, and bicarbonate solutions regarding cytotoxicity and especially intracellular acidification will hopefully shed new light on the toxic properties of these solutions.