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α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria

Nature Medicine volume 23, pages 288–290 (2017)Cite this article

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Abstract

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1−/− mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

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Figure 1: α-Lipoic acid inhibits cystine stone formation in the Slc3a1−/− mouse model of cystinuria.
Figure 2: α-Lipoic acid increases cystine solubility in the urine environment.

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Acknowledgements

We thank R. Murphy and S. Melov for their advice regarding μCT; T. Te Koi for histology assistance; M. Chamoli and N. Mathew for help with imaging; and D. Chrzan for helpful discussions. This work was supported by grants from the American Federation of Aging Research (to P.K.), the Larry L. Hillblom Foundation (to P.K.), the Boston Scientific Foundation (to M.L.S.), and the NIH (R01 AG038688 and R01 AG045835 to P.K.; R21 DK091727 to P.K. and M.L.S.; P20 DK100863 and R21 DE025961 to M.L.S.; K12 DK083021 and R21 DK109433 to T.C.).

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Author notes

  1. Marshall L Stoller and Pankaj Kapahi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, University of California, San Francisco, San Francisco, California, USA

    Tiffany Zee, Neelanjan Bose, Jennifer N Beck, David W Killilea, Thomas Chi, Marshall L Stoller & Pankaj Kapahi

  2. Buck Institute for Research on Aging, Novato, California, USA

    Tiffany Zee, Neelanjan Bose, Jennifer N Beck, See Yang, Sruthi Damodar, David Hall, Monique N O'Leary, Arvind Ramanathan, Arnold Kahn & Pankaj Kapahi

  3. Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA

    Jarcy Zee

  4. Division of Urology, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA

    Jaspreet Parihar

  5. Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA

    Min Yang, Jay Tischfield & Amrik Sahota

  6. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA

    Roy R Gerona

  7. Nutrition and Metabolism Center, Children's Hospital of Oakland Research Institute, Oakland, California, USA

    David W Killilea

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  1. Tiffany Zee
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Contributions

T.Z., A.K., M.L.S., and P.K. conceived the experiments. T.Z. and N.B. developed methodology and designed experiments. T.Z., N.B., and J.Z. analyzed and interpreted data. T.Z., J.N.B., S.Y., J.P., M.Y., and S.D. performed in vivo experiments. N.B., T.Z., D.H., and A.R. performed ex vivo and in vitro experiments. M.N.O'L. and T.Z. performed food and water intake measurements. J.T. and A.S. designed and generated the Slc3a1−/− mouse. T.Z., N.B., and J.Z. wrote the manuscript, and D.W.K., A.S., R.R.G., T.C., A.K., M.L.S., and P.K. revised the manuscript.

Corresponding authors

Correspondence to Marshall L Stoller or Pankaj Kapahi.

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The authors declare no competing financial interests.

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Zee, T., Bose, N., Zee, J. et al. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Med 23, 288–290 (2017). https://doi.org/10.1038/nm.4280

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