We compared the effects of dialysate composition on changes in intermediary metabolites, acid-base balance, and potassium removal during hemodialysis. Patients were dialyzed against dialysates containing acetate or bicarbonate, each with or without glucose, in a four-way cross-over study. Dialysates containing acetate were associated with significant perturbations in intermediary metabolism, including increases in blood citrate, acetoacetate and beta-hydroxybutyrate and a decrease in pyruvate. In contrast, bicarbonate-containing dialysates caused minimal perturbations in intermediary metabolism. Addition of glucose to the dialysate decreased the changes in intermediary metabolites; however, the magnitude of this effect was less than that observed for the change from acetate to bicarbonate. Use of acetate also resulted in lower post-dialysis blood-concentrations of base equivalents than obtained with bicarbonate; this difference was unaffected by the presence or absence of glucose. Although pre- and post-dialysis potassium concentrations were unaffected by the dialysate formulation, total potassium removal was significantly greater when glucose was omitted from the dialysate. Our results suggest that both bicarbonate and glucose should be included in the dialysate, particularly for those patients whose capacity for metabolism may be limited because of highly efficient dialysis, intercurrent illness, or starvation. However, addition of glucose to the dialysate may require a reduction in dialysate potassium to maintain proper potassium homeostasis.

Recommended culture methods for monitoring bacterial contamination of H₂O, dialysate and bicarbonate concentrate in dialysis centers in the USA involves culturing these fluids for 48 h at 37 °C. A variety of media and commercial culture methods are accepted for monitoring these fluids. Over a 3 month period a comparison was made between an acceptable culture method, tryptic soy agar (TSA) employing the pour plate (PP) technique at 37 °C for 48 h, and PP cultures on standard methods agar (SMA) and R2A agar, incubated at ambient temperature (23°C) for 48, 72, 168 h. Increases in the colony counts over time occurred for all three fluids. However, counts were greater on SMA and R2A than on TSA. The increases over the standard 48-hour TSA cultures ranged as high as 10⁴ times for 23°C cultures at 7 days of incubation. Endotoxin levels even in the most contaminated samples were found to be below the acceptable 5 EU/ml recommended for reprocessor water. Bacterial colonies that appeared at 48, 72 and 168 h were isolated and identified. Pseudomonas, Moraxella, Acinetobacter and CDC group VI C-2 were among some of the common bacteria isolated. This study indicates that the media utilized, the time and temperature of incubation may result in a significant underestimation of the bacterial population of water and dialysis fluids, thus potentially placing the patient at a higher risk.

This study evaluated the acid-base and metabolic effects of several organic anions which might have application in the correction of metabolic acidosis during hemodialysis. Anesthetized dogs were infused intravenously with the sodium salts of either chloride, bicarbonate, acetate, lactate, or pyruvate. Acetate perturbated metabolism more than any of the other organic anions infused. These perturbations included hypoxemia, reductions in serum potassium and phosphorus, a decrease in plasma, glucose, and increases in intermediary metabolites such as lactate, acetoacetate and beta-hydroxybutyrate. Transferance of our findings to hemodialysis suggests that acetate would compromise the ability of dialysis to reduce body burdens of potassium and phosphorus and provide proper base repletion. Pyruvate would appear superior to acetate as a base substitute by virtue of its lesser effects on oxygen consumption and electrolyte distribution and its capacity to produce glucose. However, the significant production of lactate with pyruvate infusion, coupled with diffusive losses of bicarbonate during dialysis and the possible instability of pyruvate in solution, would still hinder proper base repletion. Bicarbonate generation with lactate infusion was too slow to provide a practical alternative for base repletion in hemodialysis. Bicarbonate infusion caused minimal alterations in intermediary metabolism. This, in conjunction with obviating diffusive losses, suggests the use of bicarbonate would allow more appropriate base repletion during hemodialysis.

No abstract

TNF-alpha enhances the response of polymorphonuclear leukocytes (PMN) to chemoattractants: however, the mechanism by which this occurs is unclear. We addressed the hypothesis that TNF-alpha enhances the PMN response to chemoattractants by increasing chemoattractant receptor transmembrane signaling, using fMLP as the model chemoattractant. fMLP-stimulated guanine nucleotide binding (G) protein activation was significantly increased in plasma membranes isolated from PMNs exposed to TNF-alpha 100 U/ml for 10 minutes (TNF-M), compared to membranes from control cells (CM). Formyl peptide receptor number and affinity were not significantly different in CM and TNF-M. Gi and Gs content were increased in TNF-M as measured by pertussis toxin and cholera toxin (CT) catalyzed ADP-ribosylation, respectively. The increased Gi was coupled to the formyl peptide receptor as shown by receptor-specific CT labeling of Gi. Immunoblot analysis showed that both G alpha i2 and G alpha 3 were increased in TNF-M. The functional activity of the increased G protein content was demonstrated by increased NaF-stimulated phospholipase D activity in TNF-alpha-treated PMNs. We conclude that TNF-alpha rapidly stimulates increased PMN plasma membrane expression of G proteins that couple formyl peptide receptors to effector enzymes. Regulation of G protein expression may be a significant mechanism by which TNF regulates PMN function.