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- W3023681229 abstract "You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I (PD04)1 Apr 2020PD04-02 EXPERIMENTAL EVIDENCE OF HEIGHTENED RISKS OF RENAL CALCINOSIS AND STONE FORMATION IN MICE TREATED WITH ANTIBIOTICS AND UNDER HYPEROXALURIA Yan Liu*, Ellen Shapiro, Herbert Lepor, and Xue-Ru Wu Yan Liu*Yan Liu* More articles by this author , Ellen ShapiroEllen Shapiro More articles by this author , Herbert LeporHerbert Lepor More articles by this author , and Xue-Ru WuXue-Ru Wu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000824.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although a recent population-based, randomized, controlled study showed a strong correlation between oral antibiotic use and risks of nephrolithiasis, experimental evidence directly linking antibiotic use, gut microbiome and renal calcinosis is lacking. By treating normal mice with broad-spectrum antibiotics on controlled schedules and by placing them under normoxaluric or hyperoxaluric condition, we studied the effects of antibiotics on urine oxalate levels and renal calcinosis. METHODS: An established antibiotic treatment protocol for mice (1 g/L each of ampicillin, neomycin, metronidazole and 0.5 g/L of vancomycin) was adapted for this study. Male mice (2-month old, 129/SvEv strain) were randomized into 6 groups and fed with drinking water for 30 days containing: (1) no 5% hydroxyl-L-proline (HLP) or antibiotics (n=7); (2) antibiotics only (n=6) (3) HLP only (n=5); (4) HLP and antibiotics simultaneously (n=5); (5) HLP immediately after antibiotics (n=5); and (6) HLP 4 weeks after antibiotics (n=12). Renal calcinosis was assessed by von Kossa staining. Urine oxalate (Ox) levels were determined by oxalate kit and referenced to creatinine (Cr). Fecal microbiome was quantified by Real-time PCR using primers in v4 region of 16S rDNA. RESULTS: Antibiotic treatment reduced the gut microbiome by 90% and raised urine oxalate level (0.53 mg/mg (Ox/Cr) in Group 2, compared to 0.31 mg/mg in Group 1). HLP (Group 3) alone raised urine oxalate level to 0.65 mg/mg. However, no renal calcinosis was detected in Groups 2 and 3, neither was with Group 1. Concurrent antibiotics and HLP (Group 4) caused the highest increase of urine oxalate (1.15 mg/mg), and this was accompanied by renal papillary calcification and renal pelvic stone in 100% and 40% of the mice, respectively. HLP immediately after (Group 5) or 4 weeks after antibiotic exposure (Group 6) also caused high urine oxalate (0.85 mg/mg and 0.78 mg/mg, respectively), and renal papillary crystals in 60% and 53% of the mice, respectively. This occurred despite the fact that Group 6 mice had recovered 69% of total gut microbiome, compared to Group 1 mice. CONCLUSIONS: Our data strongly suggest that antibiotic-caused reduction of gut microbiome can increase the concentrations of urine oxalate; that renal calcification and stone formation after antibiotic exposure occur only under extreme hyperoxaluric conditions; and that antibiotic-induced microbiome dysbiosis may not be restored naturally and quickly, and the increased risks of nephrolithiasis may be long-lasting. Our study sets a stage for us and others to further explore the identity and the functional effects of gut microbiome on oxalate homeostasis and nephrolithiasis. Source of Funding: NIH © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e78-e78 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yan Liu* More articles by this author Ellen Shapiro More articles by this author Herbert Lepor More articles by this author Xue-Ru Wu More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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- W3023681229 title "PD04-02 EXPERIMENTAL EVIDENCE OF HEIGHTENED RISKS OF RENAL CALCINOSIS AND STONE FORMATION IN MICE TREATED WITH ANTIBIOTICS AND UNDER HYPEROXALURIA" @default.
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