Basic Science: Stones
Moderated Poster Session
MP2-2 - Reduction of Urinary Oxalate by Enzymatic Reduction of Dietary and Endogenous Oxalate
Thursday, September 20
4:00 PM - 6:00 PM
Location: Room 242B
Victoria Bird, MD
Assistant Professor of Urology, Affiliate Professor of Biomedical Engineering, Director
U. of Florida, College of Medicine and College of Engineering, National Medical Association and Research Group LLC
Introduction & Objective : Introduction: Elevated excretion of urinary oxalate continues to be a condition that affects more than 30% of the kidney stone forming population. Objective: Our aim was to develop an oral agent that that is able to enzymatically reduce urinary oxalate by way of intercepting oxalate in both the stomach (diet) and the intestines (endogenous).
Methods : A0 is an orally administered recombinant oxalate decarboxylase (OxDC) enzyme from Agrocybe aegerita, designed to degrade oxalate at different pH ranges (throughout the entire length of the gastrointestinal tract, GI tract). An IACUC approved study was conducted in male Gottingen pigs to evaluate the effects of administering A0 on the urinary response to oxalate loading (dietary: 150 mg of oxalate per meal, days 0-9) and hydroxyproline (HP) (endogenous, days 13-22). Eight Pigs were administered 344 mg of A0 (~5000 units of activity) about 15 minutes after consuming either a high oxalate diet or a low oxalate 5% HP diet, twice per day, followed by urine sample collection (24 hour total collection). Animals were housed individually and placed in metabolic cages on days that required urine collection. Urine was collected in acid to ensure slowed oxalogenesis from ascorbic acid and other oxalate precursors in urine. All animals received the antibiotic oral gentamicin (2 mg/kg) two weeks prior to and throughout the duration of the study, to ensure that the animals were not colonized by Oxalobacter formigenes.
Results : A0 dosing decreased urinary oxalate excretion. The administered dose of A0 was capable of reducing urinary oxalate excretion by 71% from the dietary phase [dosing days – low oxalate diet (LOD) days] and 45% during the endogenous phase (dosing days – LOD days). A0’s effectiveness is the result of its high catalytic efficiency, Km between 50-250 mM and a broad active pH profile, pH 1.5-7.5. There were no side effects noted (body weight, clinical observations, food consumption etc).
Conclusions : Oral agent A0 is able to reduce urinary oxalate levels, regardless of oxalate source (dietary or endogenous).