Cystinuria: genetic aspects, mouse models, and a new approach to therapy

Amrik Sahota, Jay A. Tischfield, David S. Goldfarb, Michael D. Ward, Longqin Hu

Research output: Contribution to journalReview articlepeer-review


Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Males generally are more severely affected than females. The disorder may lead to chronic kidney disease in many patients. The cystine transporter (b 0,+ ) is a heterodimer consisting of the rBAT (encoded by SLC3A1) and b 0,+ AT (encoded by SLC7A9) subunits joined by a disulfide bridge. The molecular basis of cystinuria is known in great detail, and this information is now being used to define genotype–phenotype correlations. Current treatments for cystinuria include increased fluid intake to increase cystine solubility and the administration of thiol drugs for more severe cases. These drugs, however, have poor patient compliance due to adverse effects. Thus, there is a need to reduce or eliminate the risks associated with therapy for cystinuria. Four mouse models for cystinuria have been described and these models provide a resource for evaluating the safety and efficacy of new therapies for cystinuria. We are evaluating a new approach for the treatment of cystine stones based on the inhibition of cystine crystal growth by cystine analogs. Our ongoing studies indicate that cystine diamides are effective in preventing cystine stone formation in the Slc3a1 knockout mouse model for cystinuria. In addition to crystal growth, crystal aggregation is required for stone formation. Male and female mice with cystinuria have comparable levels of crystalluria, but very few female mice form stones. The identification of factors that inhibit cystine crystal aggregation in female mice may provide insight into the gender difference in disease severity in patients with cystinuria.

Original languageEnglish (US)
Pages (from-to)57-66
Number of pages10
Issue number1
StatePublished - Feb 5 2019


  • Crystal growth inhibitors
  • Cystine
  • Cystinuria
  • Mouse models
  • Therapeutics
  • Transport defect

ASJC Scopus subject areas

  • Urology


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