Renal Tubular Reabsorption of Acetoacetate in the Dog

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Abstract
A study was made of the renal tubular reabsorption of acetoacetate ion in the normal dog over a wide range of plasma acetoacetate concns. The aniline citrate method of Edson was adapted to the analysis of acetoacetate in plasma filtrates and urine. Glomerular filtration rate was measured by the creatinine clearance. It was found that acetoacetate is a threshold substance, being almost completely reabsorbed at normal plasma concns. As the filtered load increases up to a level of approx. 0.5 m.eq./min./sq.m., reabsorption is essentially complete. Further increases in filtered load exceed a max. rate of reabsorption of around 0.4 m.eq,/ min./sq.m. As the filtered load is increased above 0.9 m.eq./ min./sq.m., the rate of reabsorption shows a progressive decline until it amts. to only about 0.1 m.eq./min./sq.m. It was shown that this declining rate of tubular reabsorption was not related to urine flow, acid base balance, or competitive inhibition by beta-hydroxybutyrate. It was postulated that it was the result of an auto-inhibition of some enzyme system in the tubular cells critical for the acetoacetate reabsorptive mechanism. Evidence was presented to support the view that approx. 50% of the "reabsorbed" acetoacetate could be utilized by the renal tubules. It was pointed out that the question of transport vs. utilization should be reexamined for metabolites excreted by the kidney.

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