Urinary excretion of amino acids in normal and cystinuric dogs

The 24-h urine excretion of 20 amino acids was investigated in 24 cystinuric and 15 normal dogs. The diagnosis of cystinuria was based on infrared spectroscopy of removed uroliths, which in all cases were composed of pure cystine. Seven of 24 cystinuric dogs showed normal cystine excretion compared to normal dogs, and four of 24 dogs showed normal total amino acid excretion. In contrast to earlier investigations, almost half of the cystinuric dogs (46%) showed elevated excretion of five or more amino acids. Isolated cystinuria, or isolated dibasic amino aciduria was not found. Compared to normal dogs, the cystinuric dogs showed a significantly (P < 0.05) increased excretion of cystine, arginine, lysine, cystathionine, glutamic acid, threonine and glutamine. There was a significant correlation (P < 0.05) between the urinary excretion of cystine and 10 other amino acids, with the highest correlation found (P < 0.001) for arginine, lysine, cystathionine, ornithine and 1-methyl-histidine. Three patterns of amino acid excretion could be identified: (1) increased excretion and a significant correlation with cystine for the three dibasic amino acids (lysine, arginine and ornithine), compatible with a common reabsorption mechanism as shown in man. This pattern was also found for cystathionine and glutamic acid, which might indicate a relation in metabolism or transport; (2) increased excretion but no correlation with cystine for glutamine, threonine and citrulline; (3) good correlation with cystine, but no increased excretion for 1-methyl-histidine, phenylalanine, 3-methyl-histidine, leucine and alanine. The great variation in urinary cystine excretion suggests that factors other than the excretion of cystine must be considered as causes of cystine urolith formation. For example, cystinuric dogs were found to have lower diuresis than normal dogs and produced urine with higher cystine concentration thereby increasing the risk of cystine urolith formation.