PHARMACOKINETICS OF ESSENTIAL AMINO-ACIDS IN CHRONIC DIALYSIS PATIENTS

Possible disorders of essential amino acid (EAA) metabolism in maintenance dialysis patients (D) were studied by measuring plasma amino acids before and sequentially after administering a mixture of 8 EAA po and iv. The EAA were in a ratio similar to that required for optimal utilization, and the total dose given was within physiological range. Ten D and six normals (N) received 150 mg/kg po as a 10.5 g/dl solution and 117 mg/kg iv as a 5.1 g/dl solution infused at a constant rate of 4 mg/kg per min. Blood glucose and immunoreactive insulin were also measured. Both D and N were postabsorptive and at least 18 hr postdialysis. The fraction of the oral dose appearing in the systemic circulation was quite variable for each EAA in both N and D. Total body clearance was significantly lower in D (P<0.05) for threonine, phenylalanine, valine, leucine, and isoleucine and this difference could not be explained by changes in renal excretion. The apparent volume of distribution did not differ between N and D for all EAA except for valine and phenylalanine. Blood glucose and insulin varied only slightly in both N and D. These studies indicate that there are a variety of significant abnormalities in the metabolism of specific EAA in D. Decreased total body clearance of the branched-chain amino acids, since they are primarily metabolized by muscle, may result from a defect in muscle metabolism in D.