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

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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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.

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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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