Renal handling of diamino acids in lysinuric protein intolerance.
Lysinuric protein intolerance (LPI) is a rare recessively inherited disease in which one of the fundamental physiological defects is in the mechanism by which diamino acids are transported by the kidney. The purpose of the present studies was to examine that mechanism in four controls and seven patients with LPI. Two types of studies were conducted. In the first set, the renal handling of l-arginine and l-ornithine was evaluated by gradually increasing the plasma concentration of each of these amino acids by constant infusion techniques. In the second set of studies, the possible existence of competitive inhibition between l-arginine, l-ornithine, and l-lysine was examined. In the control subjects, there was almost complete reabsorption of arginine and ornithine, with increases in their filtered loads to 50-100 times normal. With further increases in the filtered loads of these amino acids, there was a gradual decrease in their fractional reabsorption. Mutual competitive inhibition was suggested by the observation that an increase in the filtered load of one diamino acid was associated with a decrease in the reabsorption of the other two. In LPI, the fasting plasma diamino acid concentrations were significantly lower than in the controls. With low filtered loads, the fractional reabsorption of the diamino acids was clearly below normal. This defect diminished with higher loads. A stepwise increase in the plasma concentration of one diamino acid resulted in a biphasic response. Initially, net tubular secretion of the other diamino acids was noted, but later was followed by return to net absorption. When two diamino acids were infused simultaneously, net absorption of both took place, though less efficiently than in the controls. We conclude that the renal reabsorption mechanism is defective in patients with LPI. With low normal filtered loads, there is increased fractional excretion of all three diamino acids resulting in low serum concentrations of these compounds. However, at higher artificially elevated concentrations of diamino acids, the capacity of the renal transport system in these patients appears normal.
D000293:Adolescent; D000328:Adult; D000599:Amino Acids, Diamino / Q000097:blood / Q000652:urine*; D001120:Arginine / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004044:Dietary Proteins / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005808:Genes, Recessive; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D007684:Kidney Tubules / Q000378:metabolism*; D008239:Lysine / Q000097:blood / Q000652:urine*; D008297:Male; D009952:Ornithine / Q000097:blood / Q000652:urine; D000608:Renal Aminoacidurias / Q000097:blood / Q000652:urine*; D014508:Urea / Q000096:biosynthesis
D000599:Amino Acids, Diamino; D004044:Dietary Proteins; D014508:Urea; D001120:Arginine; D009952:Ornithine; D008239:Lysine