Inulin and Endogenous Amino Acid Renal Clearances

Cystinuria is manifested by cystine calculi and high urinary excretion of cystine (2), lysine, arginine (3), and ornithine (4). Abnormally low plasma levels have been established for cystine (5, 6), lysine (7), arginine, and ornithine (5, 8). Several investigators have previously demonstrated increased renal clearances for cystine, lysine, arginine, and ornithine (7-11). These four amino acids each have two amino groups separated by 4 to 6 carbon atoms. This led Dent and Rose to suggest that a common enzymatic mechanism for their renal tubular reabsorption is missing in cystinuria (11). Further support for this hypothesis was provided by the demonstration that intravenous infusion of lysine produced increased excretion of cystine and arginine in nomal individuals but not in those with cystinuria (7, 10). In addition to the four amino acids previously mentioned, studies in this laboratory have recently demonstrated that significant amounts of the asymmetrical disulfide of L-cysteine and L-homocysteine were excreted by all of 10 patients with classical cystinuria (12). This substance was recorded by Stein as a peak in the isoleucine area of the ion-exchange chromatogram (4). He determined the relative molar excretion of cystine, arginine, lysine, and ornithine in the urine of five patients with cystinuria, without reference, however, to plasma concentrations or renal func-