Recurrent Cystine Research Articles

Recurrent Cystine Stones in Both Kidneys

Recurrent Cystine Stones in Both Kidneys

Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria

Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mutations, we have delineated the complete genomic organization of the SLC3A1 coding region using polymerase chain reaction strategies. The complete coding region of the gene is contained within a single yeast artificial chromosome clone and consists of 10 exons and 9 introns. Oligonucleotide primers capable of amplifying selected exons have been made and used in mutational analysis of DNA from 24 cystinuria probands. We illustrate the usefulness of this approach by identifying two novel SLC3A1 mutations. One novel mutation causes replacement of a highly conserved arginine residue (arginine-452) with tryptophan in the cytoplasmic loop between the putative third and fourth membrane spanning segments. A second previously unreported mutation results in replacement of a highly conserved tyrosine (tyrosine-461) residue with histidine in the same region of the protein. In addition, we detected three previously reported SLC3A1 mutations, R270X, 1500 +1/G to T, and M467T, the latter being present in approximately 20% of cystinuria chromosomes examined. Our findings provide a foundation for the development of more accessible diagnostic screening assays for detecting SLC3A1 mutations using patient genomic DNA, and also contribute to the emerging spectrum of cystinuria genotypes.

Dietary Restriction of Sodium as a Means of Reducing Urinary Cystine

We assessed 5 patients with recurrent cystine urolithiasis before and after implementation of a low sodium diet. This diet led to a significant decrease in the 24-hour urinary excretion of sodium and cystine. Dietary restriction of sodium should be an important component of the therapeutic strategy of patients with cystinuria.

Repeated Percutaneous Nephrolithotomy in Patient with Recurrent Cystine Lithiasis: Preservation of Renal Function

Cystinuria places the patient at continual risk for urinary tract stone formation. Despite aggressive medical therapy, multiple stone recurrences are common, and surgical intervention is often required. Historically, repeated open procedures have been associated with high morbidity. Extracorporeal shock wave lithotripsy has a disappointing record against cystine stones, and percutaneous nephrolithotomy has evolved into the optimal form of surgical therapy for these patients. We report on a patient whose recurrent unilateral cystine calculi necessitated four percutaneous nephrolithotomies with excellent preservation of renal anatomy and function. This result compares favorably with those obtained from repeated open stone procedures in the cystinuric population.

Mercaptopropionylglycine: A Progress in Cystine Stone Therapy

During a 4-year period 9 cases of severe recurrent cystine stones and cystinuria were treated with mercaptopropionylglycine. The oral long-term administration revealed the high effectiveness of the drug and resulted in no further stone formation. Mercaptopropionylglycine is free of side effects and more effective than D-penicillamine.