Amino Acid Extraction and Ammonia Metabolism by the Human Kidney During the Prolonged Administration of Ammonium Chloride*

Abstract

According to current concepts, renal ammonia synthesis may be attributed to the renal extraction and catabolism of certain plasma amino acids. In 1943, Van Slyke and associates demonstrated in the dog that the amide nitrogen of glutamine was removed from arterial plasma in quantities sufficient to account for approximately 60 per cent of the urinary ammonia excreted during metabolic acidosis (1). It was proposed that the remaining 40 per cent of urinary ammonia could be accounted for by the renal uptake of plasma a-amino nitrogen. In agreement with this hypothesis, many investigators have since shown that the administration of several amino acids other than glutamine is associated with an increased urinary ammonia excretion (2-4). Loading experiments of this type have indicated thatbesides glutamine-glycine, alanine, asparagine, leucine. and histidine may serve as precursors of urine ammonia. The demonstration of appropriate enzyme systems within renal tissue capable of forming ammonia from these substrates has been offered as additional support for the thesis that several plasma amino acids may participate normally in the renal production of ammonia. Nevertheless, the specific amino acids that serve as renal ammonia precursors have not been identified clearly in conditions associated with normal acid-base balance and normal plasma amino acid concentrations. The present study was undertaken for two principal reasons: first, to characterize the' typical patterns of uptake or release * Investigation supported in part by U. S. Public Health Service research grants A-5930 and A-6306 from the National Institutes of Health, Bethesda, Md., and by the Veterans Administration Clinical Investigator Program; presented in part at the annual meeting of the Southern Section, Amer. Fed. Clin. Research, New Orleans, La., January 18, 1962. of individual amino acids by the normal human kidney, and second, to determine whether or not the adaptive increase of renal ammonia production during metabolic acidosis could be attributed to chances in the renal extraction of certain plasma amino acids. METHODSTwelve renal clearance experiments were carried out on eleven healthy male volunteers between 21 and 38 years old. All studies were conducted with them in the recumbent position after an overnight fast. To facilitate the collection of timed urine specimens, urine flows of approximately 5 ml per minute were assured by the oral ingestion of 500 ml of tap water 1 hour before the test, followed immediately by a constant intravenous infusion of 5 per cent dextrose in water. After appropriate priming doses, an-intravenous maintainance infusion of a solution of inulin and para-aminohippurate (PAH) was begun 45 minutes before the first clearance period via a Bowman constant-infusion pump. During the equilibration period, a no. 7 or 8 cardiac catheter was introduced into a renal vein through either the right brachial or femoral vein under fluoroscopic control. An indwelling Cournand arterial needle was placed in the left brachial artery. Thr...

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