Acetate Metabolism in Normal Human Subjects

Abstract

Acetate is used as the source of bicarbonate during hemodialysis. The purpose of the present experiments was to determine the metabolic consequences of acute acetate infusion, the fractional generation of bicarbonate from acetate, and the kinetics of acetate administration in normal human subjects. Experiment I consisted of two infusions, administered on separate occasions to 10 healthy adult volunteers, of 4 mmoles/kg body weight Na acetate or Na bicarbonate. Each infusion was administered intravenously during 1 hr. All subjects tolerated the infusions well. The plasma protein concentrations abruptly fell, reflecting hemodilution. After correcting for hemodilution there was no change in plasma creatinine, urea, uric acid, alkaline phosphatase, SGPT, LDH, cholesterol, or triglycerides. Acetate infusion produced a significant rise in plasma pyruvate, lactate, and α-hydroxybutyrate concentrations. Both acetate and bicarbonate infusions produced an alkalosis and a marked alkalemia. In addition, plasma potassium, calcium, and phosphate concentrations fell; these changes are attributed to the alkalosis. Prior to the acetate infusion the mean urinary acetate concentration was 0.085 ± 0.013 mM. Acetate infusions increased urinary acetate concentration to 9.4–13.3 mM. The fractional excretion of acetate rose to approximately 40% during the infusion suggesting that reabsorption of filtered acetate may be inhibited by volume expansion and/or alkalosis. The mean ± SEM for the bicarbonate space, determined from the bicarbonate infusions, was 54 ± 10% of body weight. The mean fractional generation of bicarbonate from acetate, determined from the acetate infusions was 100 ± 21%. Prior to the infusions the mean venous plasma acetate concentration was 0.040 ± 0.010 mM. During the acetate infusion, venous plasma acetate rose to a maximum of 2.12 ± 0.29 mM. During the last 30 min of the infusion, plasma acetate concentrations appeared to reach a steady state. Following termination of the infusion, the acetate concentrations rapidly diminished. Kinetic modeling of these results indicated that acetate disposition was best accounted for by a two-compartment model with first order elimination from the first compartment. To test the validity of this model, Experiment II was performed. Ten healthy adult volunteers were infused with 1, 2, and 4 mmoles of Na acetate during 1 hr on three separate occasions. Kinetic analysis of the plasma acetate concentrations indicated that the data were best fit by a two-compartment model with first order elimination. The mean metabolic clearance rate of acetate was 2.31 ± 0.21 liter/min. It is concluded from these experiments, that acetate is rapidly metabolized, generating equimolar amounts of bicarbonate. The major metabolic effects of acetate administration are related to the development of alkalosis. Acetate metabolism in normal human subjects appears to be first order. However, higher blood acetate concentrations may be achieved during hemodialysis and further studies are indicated to investigate the kinetics of acetate metabolism during hemodialysis.