Original article| Volume 102, ISSUE 4, P536-542, October 1983

The impact of acetazolamide on renal ammoniagenesis and gluconeogenesis

  • Richard L. Tannen
    Reprint requests: Richard L. Tannen, M.D., Internal Medicine (Nephrology), D3238 South Ambulatory Care Building, The University of Michigan, Ann Arbor, Mich. 48109.
    From the Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich., USA

    From the Radcliffe Infirmary, Oxford, England
    Search for articles by this author
  • Brian D. Ross
    From the Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich., USA

    From the Radcliffe Infirmary, Oxford, England
    Search for articles by this author
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      In view of recent reports suggesting that acetazolamide (ACZ) inhibits renal ammoniagenesis and the pentose phosphate pathway, its effects on renal metabolism were investigated with rat isolated perfused kidney and isolated cortical tubules. In the isolated kidney perfused with glutamine (2 mM) and glucose (5mM), ACZ (0.1 mM) resulted in a natriuresis and bicarbonate diuresis and decreased NH3 production from 1.72 to 1.35 μmol/min/gm dry weight (p < 0.05). NH3 production was unchanged in control perfusions in which no inhibitor was added. With kidneys from acidotic animals perfused with glutamine (2 mM) without glucose, NH3 production was unaltered by ACZ but glucose production decreased from 0.93 to 0.20 μmol/min/gm (p < 0.01). ACZ inhibited NH3 (14.2 to 12.6 μmol/min/gm, p < 0.01) and glucose (1.6 to 1.2 μmol/min/gm, p < 0.05) and stimulated glutamate (2.2 to 2.9 μmol/min/gm, p < 0.01) production by isolated tubules from normal rats incubated with 2 mM glutamine and had similar effects with acidotic animals. Glucose production from malate was also inhibited. The increase in glutamate and decrease in glucose production from glutamine, as well as malate, suggest that ACZ inhibits ammoniagenesis by altering metabolism of the glutamine carbon skeleton rather than by affecting glutamyl transferase. Finally, these results emphasize that ACZ has definite effects on renal metabolism, which must be considered in interpreting studies using it to elucidate hydrogen ion transport.


      glomerular filtration rate ((GFR))
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