The medical and metabolic consequences of administration of sodium acetate.

1. The standard total parenteral nutrition, peritoneal dialysis, hemodialysis and many surgical fluids in use today contain 36 to 45 mM D,L-lactate or 2 to 140 mM acetate whereas the normal blood level of D-lactate is 0.02 mM L-lactate 0.5 to 5 mM and acetate 0.1 nM. The reasons for the continued use in patients of such unphysiological concentrations of these anions appear to be historic. 2. Administration of similar concentrations of these anions to the rat causes widespread metabolic disturbances which mimic many of the untoward complications associated with current parenteral and dialysis therapy. Understanding of the mechanisms attendant upon the metabolism of these anions may serve as a guide for designing improved parenteral fluids for human patients. 3. Elevation of blood D-lactate to 5 mM is associated with cerebral dysfunction in human patients. 4. Acetate stimulates the release of the inflammatory leukokine, interleukin-1 from human monocytes. Use of 35 to 45 mM acetate in peritoneal dialysis fluids led to peritoneal fibrosis. Patients exposed to acetate containing hemodialysis fluids have 12-fold elevation in their plasma interleukin-1 levels. 5. Administration of 20 mM sodium acetate to rats leads to a number of metabolic disturbances similar to those seen in human dialysis patients: (a) Acetate elevates blood glucose in the rat and may contribute to the exacerbation of the carbohydrate intolerance seen in uremic patients. (b) Acetate increases the levels of hepatic malonyl CoA, the rate controlling substrate of fatty acid synthesis and may exacerbate the hypertriglyceridemia characteristic of dialysis patients. (c) Acetate administration in the rat leads to a decrease in the cytosolic phosphorylation potential, reduction of the redox state of the free cytosolic NAD couple and paradoxical oxidation of the mitochondrial NAD couple in a pattern analogous to that produced by uncouplers of oxidative phosphorylation and may account in part for the elevation of temperature reported in patients undergoing hemodialysis with acetate. (d) Acetate administration in the rat leads to an increase in intracellular phosphorylated intermediates, adenine nucleotides, inorganic phosphate, inorganic pyrophosphate, calcium and magnesium. On cessation of acetate metabolism, the inorganic phosphate and calcium accumulated intracellularly leave the intracellular space. In patients undergoing hemodialysis, the blood phosphate returns to predialysis levels, within 6 hr after the completion of treatment, leaving significant numbers of patients with chronic hyperphosphatemia and the multiple complications attendant to that state.(ABSTRACT TRUNCATED AT 400 WORDS)