MP12-12 ?-LIPOIC ACID SUPPRESSES CYSTINE STONE FORMATION IN A GENETIC MOUSE MODEL OF CYSTINURIA

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2017MP12-12 ?-LIPOIC ACID SUPPRESSES CYSTINE STONE FORMATION IN A GENETIC MOUSE MODEL OF CYSTINURIA Tiffany Zee, Neelanjan Bose, Jarcy Zee, Jennifer Beck, See Yang, Jaspreet Parihar, Min Yang, Sruthi Damodar, David Hall, Monique O'Leary, Arvind Ramanathan, Roy Gerona, David Killilea, Thomas Chi, Jay Tischfield, Amrik Sahota, Arnold Kahn, Pankaj Kapahi, and Marshall Stoller Tiffany ZeeTiffany Zee More articles by this author , Neelanjan BoseNeelanjan Bose More articles by this author , Jarcy ZeeJarcy Zee More articles by this author , Jennifer BeckJennifer Beck More articles by this author , See YangSee Yang More articles by this author , Jaspreet PariharJaspreet Parihar More articles by this author , Min YangMin Yang More articles by this author , Sruthi DamodarSruthi Damodar More articles by this author , David HallDavid Hall More articles by this author , Monique O'LearyMonique O'Leary More articles by this author , Arvind RamanathanArvind Ramanathan More articles by this author , Roy GeronaRoy Gerona More articles by this author , David KillileaDavid Killilea More articles by this author , Thomas ChiThomas Chi More articles by this author , Jay TischfieldJay Tischfield More articles by this author , Amrik SahotaAmrik Sahota More articles by this author , Arnold KahnArnold Kahn More articles by this author , Pankaj KapahiPankaj Kapahi More articles by this author , and Marshall StollerMarshall Stoller More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.434AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cystinuria is a disorder characterized chronic kidney stone formation and caused by genetic mutations in the heterodimeric cystine transporter (SLC3A1 and SLC7A9) that is responsible for cystine reabsorption. Individuals afflicted with cystinuria are often treated by hyper-hydration, urine alkalization, and/or pharmacological interventions aimed at increasing cystine solubility in urine. However, these treatments are limited in their effectiveness and often have serious adverse side effects. The objective of this study is to use a mouse model of cystinuria to identify novel approaches towards the treatment of cystinuria. METHODS Methods: Using longitudinal micro-computed tomography, Slc3a1-/- mouse cystine bladder stone formation was calculated at growth rate of approximately 1 mm3/day. This measure was used to evaluate interventions aimed at attenuating stone growth. A linear mixed model with random intercept was used to assess stone growth rates between treated versus control mice. RESULTS Lipoic acid was found to be a potent inhibitor of cystine stone formation in a Slc3a1-/- mouse model of cystinuria. Treatment with lipoic acid attenuated existing cystine stone growth, and prevented stone formation in young Slc3a1-/- mice. The inhibitory effect was found to be dose-dependent, and independent of lipoic acid effects on the antioxidant response pathway. Ex vivo cystine precipitation analysis revealed that lipoic acid treatment increased cystine solubility in urine. CONCLUSIONS Treatment with the nutritional supplement lipoic acid protects against stone formation in a mouse model of cystinuria. This result identifies a novel application of lipoic acid that increases urinary cystine solubility independently of pH, and may highlight a new avenue for understanding treatment strategies for cystinuric patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e149 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tiffany Zee More articles by this author Neelanjan Bose More articles by this author Jarcy Zee More articles by this author Jennifer Beck More articles by this author See Yang More articles by this author Jaspreet Parihar More articles by this author Min Yang More articles by this author Sruthi Damodar More articles by this author David Hall More articles by this author Monique O'Leary More articles by this author Arvind Ramanathan More articles by this author Roy Gerona More articles by this author David Killilea More articles by this author Thomas Chi More articles by this author Jay Tischfield More articles by this author Amrik Sahota More articles by this author Arnold Kahn More articles by this author Pankaj Kapahi More articles by this author Marshall Stoller More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...