Effect of glucose and pyruvate in acidic and non-acidic peritoneal dialysis fluids on leukocytes cell functions

Abstract

A new peritoneal dialysate containing pyruvate anions has been tested for its effects on cell functions and compared with conventional lactate and bicarbonate based solutions. The dialysate has a final pH of 5.4 to 5.6 and is composed of 1.36 to 3.86% glucose-monohydrate, 132 mmol/liter sodium, 1.75 mmol/liter calcium, 0.75 mmol/liter magnesium, 102 mmol/liter chloride and 35 mmol/liter pyruvate. For cytotoxicity testing peritoneal macrophages and peripheral blood mononuclear cells (PBMC) were exposed to conventional lactate dialysate, pyruvate dialysate, bicarbonate dialysate and a control medium RPMI 1640 (Biochrom KG, Berlin, Germany), followed by activation with different bacterial stimuli. In addition, the study further investigated the effect of varying glucose concentration in the different dialysates ranging from 0 to 3.86% and pH changes between 5.2 and 7.4 on the cytotoxicity effect on the selected cells. Mononuclear cells exposed to pyruvate-based dialysate before stimulation with endotoxin exhibited a tumor necrosis factor (TNF)-mRNA signal comparable to those of cells exposed to RPMI. In contrast, exposure to lactate-based dialysate completely inhibited TNF-mRNA synthesis. In addition, cytokine synthesis in macrophages and PBMCs after exposure to pyruvate was less inhibited when compared to the corresponding levels measured after exposure to lactate. The chemotactic response of polymorphonuclear cells and O-2 generation in all tested cell types after exposure to pyruvate was found not to be inhibited, whereas a complete inhibition was observed after exposure to lactate. The results demonstrate that cytotoxicity effects of peritoneal dialysate on cell lines can be minimized by using a new dialysate formulation containing pyruvate anions instead of lactate.

Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production

“…As quoted above, another important step in the formation or use of pyruvate is catalysed by rapid and reversible transamination reactions, for example catalysed via alanine transaminase, producing α-ketoglutarate and alanine (Cicalese et al 1996a, 1996b; Edlund and Halestrap 1988; Gardner and Leese 1988; Selvaraj and Sbarra 1966; Wiemer et al 1995). For leukocytes this is of major importance, because α-ketoglutarate, converted from pyruvate in particular, is responsible for key metabolic and synthetic roles which are essential in cellular viability (Curi et al 1988; Gabbianelli et al 2007; Mahiout et al 1997; Miwa et al 2000; Ramakrishnan et al 1998; Zhou and Yu 1998) and can be very rapidly into a precursor of numerous amino acids, synthetic metabolic intermediates as well as macromolecular synthesis (Curi et al 1989, 1988; Fuchs et al 1994; Riedel et al 1992; Serrano and Curi 1989; Venizelos and Hagenfeldt 1985). Interesting findings suggest indeed that α-ketoglutarate, which is also one of the most important intracellular nitrogen transporters, is not only a key intermediate in the TCA cycle (coming after isocitrate and before succinyl CoA) but also can replenish the cycle in anaplerotic reactions.…”

Comparative in vitro Study of Different Peritoneal Dialysis Solutions on Cytokine Production by Peripheral Blood Mononuclear Cells

“…It may be associated with the maintenance of intracellular pH close to physiological, due to its low buffering capacity, improvement of cellular glucose metabolic pathways and redox state [38,39,40], and sustainment of intracellular calcium homeostasis in high glucose concentrations. Mahiout et al [41] speculated that when pyruvate is used in the dialysate, the glucose-induced respiratory inhibition (Crabtree effect) is reduced. But Zhou [40 ]argues that exogenous pyruvate in PDS could not be an energy source for cells and also the Crabtree effect might not occur in neutrophils.…”

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

“…The in vitro suppressive effects of hyperosmolarity [4, 8, 13], high lactate concentrations [14,15,16], GDPs [6, 17, 18] and acidity [19] on various leukocyte functions are well known. In our previous study, we confirmed the importance of high lactate concentrations, GDPs and hyperosmolarity in the inhibition of leukocyte recruitment in vivo [7].…”