LBA01-08 KIDNEY STONE RISK AND ASSOCIATION WITH URINE OXALATE (UOX) LEVELS IN ENTERIC HYPEROXALURIA (EH)

Abstract

You have accessJournal of UrologyLate-Breaking Abstracts (LBA1)1 Apr 2020LBA01-08 KIDNEY STONE RISK AND ASSOCIATION WITH URINE OXALATE (UOX) LEVELS IN ENTERIC HYPEROXALURIA (EH) Charles Scales*, Christina Wyatt, Alicia Weeks, Christine Tosone, and Annamaria Kausz Charles Scales*Charles Scales* More articles by this author , Christina WyattChristina Wyatt More articles by this author , Alicia WeeksAlicia Weeks More articles by this author , Christine TosoneChristine Tosone More articles by this author , and Annamaria KauszAnnamaria Kausz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000946.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Introduction: EH occurs when fat malabsorption causes excessive oxalate absorption from the gastrointestinal (GI) tract, increasing renal oxalate load and in turn, kidney stone (KS) and chronic kidney disease (CKD) risk. The URIROX-1 RCT evaluated reloxaliase, a first-in-class oral enzyme that specifically targets and degrades oxalate within the gut, in EH. This is the first in-depth analysis of KS risk in this recently completed study and represents a robust profiling of KS risk in the EH population. Methods: URIROX-1, a Phase 3 double-blind RCT, evaluated efficacy and safety of reloxaliase (7,500 units or placebo [PBO] 3-5x/day orally for 4 weeks) in EH patients with 24h UOx = 50 mg/24h despite standard of care. The primary efficacy endpoint was percent change from baseline in 24h UOx. Secondary efficacy endpoints included proportion of subjects with = 20% reduction in 24h UOx and analysis of efficacy parameters in the bariatric surgery (BS) subgroup. Results: Reloxaliase produced a 22.6% reduction in 24h UOx vs 9.7% with PBO [difference -14.3% (p=0.0040)], with more profound effect in the BS subgroup [-16.2% (p=0.013)]. More subjects on reloxaliase (48.3%) vs PBO (31.6%) achieved a = 20% reduction in 24h UOx, with greater effect in BS (50% on reloxaliase vs 28.9% on PBO). GI adverse events were more common with reloxaliase, but most were mild or moderate in severity and no reloxaliase subject discontinued treatment as a result. Of 115 randomized subjects, 15 reported KS passage during the 8 week study, revealing a higher KS event rate (0.78/year) than anticipated by limited EH epidemiologic data available. Baseline 24h UOx levels of these 15 subjects was markedly higher (mean [median] 107.2 [98.5] mg/d vs 86.5 [77.5] mg/d). Conclusions: URIROX-1 is the first RCT examining a specific therapy targeting UOx reduction in EH, a clinically challenging and understudied population. The URIROX-1 study demonstrated a clinically meaningful reduction of 24h UOx in EH subjects on reloxaliase. Although the short duration of this study precludes assessment of its effect on KS risk, the URIROX-1 data underscores the utility of 24h UOx as a surrogate marker of KS risk and the value of the ongoing URIROX-2 adaptive design trial to quantify clinical benefits of reloxaliase with respect to KS disease progression and renal function. Source of Funding: Allena pharmaceuticals © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1022-e1022 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charles Scales* More articles by this author Christina Wyatt More articles by this author Alicia Weeks More articles by this author Christine Tosone More articles by this author Annamaria Kausz More articles by this author Expand All Advertisement PDF downloadLoading ...