Pharmacokinetics of essential amino acids in chronic dialysis patients

Abstract

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.