Reference values of urinary excretion of cystine and dibasic aminoacids: classification of patients with cystinuria in the Valencian Community, Spain.

OBJECTIVE: Cystinuria is an autosomal-recessive disorder of the kidneys and small intestine affecting a luminal transport mechanism shared by cystine, ornithine, arginine, and lysine. Three different types of cystinuria can be distinguished according to the excretion of these amino acids in urine samples. We propose cutoff values from our population as references and we present a classification of cystinuric patients using quantitative amino acid chromatography in first morning urine samples. DESIGN AND METHODS: A random sample of forty healthy subjects belonging to general population of the Valencian Community were selected as control subjects. Cystine, lysine, arginine, and ornithine were quantified by reverse-phase HPLC. Seventy-two subjects, diagnosed previously as cystinuric by the cyanide-nitroprusside test were classified. Probands excreting more than 113.12 micromol cystine per mmol of creatinine (i.e., 1,000 micromol cystine per gram of creatinine) were classified as homozygotes. Parents of homozygotes in whom excretion of amino acids were normal were classified as heterozygotes type I. Those probands showing the excretion of at least one amino acid and the sum of urinary cystine plus the basic amino acids higher than the corresponding references ranges in our population were classified as heterozygotes type II or type III (heterozygotes non-type 1).
RESULTS: We identified 24 homozygotes, 39 non-type I heterozygotes and 3 type I heterozygotes. The remaining 6 probands could not be classified. Means for cystine, lysine, arginine ornithine and their sum in homozygotes and heterozygotes non-type I were significantly (p < 0.001) in excess of the respective reference ranges. Moreover, means values in homozygotes were statistically different (p < 0.001) from heterozygotes non-type I.
CONCLUSION: Urinary excretion of cystine per mmol creatinine allow us to distinguish heterozygotes from homozygotes. However, the best discriminator to distinguish non-type I heterozygotes from normal population might be the excretion of lysine per mmol creatinine. Additional studies including characterization of appropriate haplotypes should be carried out for a more precise identification of types of cystinuria.