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

Tiffany Zee; Neelanjan Bose; Jarcy Zee; Jennifer N Beck; See Yang; Jaspreet Parihar; Min Yang; Sruthi Damodar; David Hall; Monique N O'Leary; Arvind Ramanathan; Roy R Gerona; David W Killilea; Thomas Chi; Jay Tischfield; Amrik Sahota; Arnold Kahn; Marshall L Stoller; Pankaj Kapahi

doi:10.1038/nm.4280

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

Nat Med. 2017 Mar;23(3):288-290. doi: 10.1038/nm.4280. Epub 2017 Feb 6.

Authors

Tiffany Zee^{1

2}, Neelanjan Bose^{1

2}, Jarcy Zee³, Jennifer N Beck^{1

2}, See Yang², Jaspreet Parihar⁴, Min Yang⁵, Sruthi Damodar², David Hall², Monique N O'Leary², Arvind Ramanathan², Roy R Gerona⁶, David W Killilea^{1

7}, Thomas Chi¹, Jay Tischfield⁵, Amrik Sahota⁵, Arnold Kahn², Marshall L Stoller¹, Pankaj Kapahi^{1

2}

Affiliations

¹ Department of Urology, University of California, San Francisco, San Francisco, California, USA.
² Buck Institute for Research on Aging, Novato, California, USA.
³ Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
⁴ Division of Urology, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA.
⁵ Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA.
⁶ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
⁷ Nutrition and Metabolism Center, Children's Hospital of Oakland Research Institute, Oakland, California, USA.

PMID: 28165480
PMCID: PMC5656064
DOI: 10.1038/nm.4280

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.

MeSH terms

Amino Acid Transport Systems, Basic / genetics
Amino Acid Transport Systems, Neutral / genetics
Animals
Cystine / drug effects*
Cystine / metabolism
Cystinuria / metabolism*
Disease Models, Animal
Kidney / diagnostic imaging
Kidney / drug effects*
Kidney / metabolism
Mice
Mice, Knockout
Solubility / drug effects
Thioctic Acid / pharmacology*
Urolithiasis / diagnostic imaging
Urolithiasis / metabolism*
X-Ray Microtomography

Substances

Amino Acid Transport Systems, Basic
Amino Acid Transport Systems, Neutral
Slc3a1 protein, mouse
Cystine
Thioctic Acid

Abstract

MeSH terms

Substances

Grants and funding