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

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.