WCE 2018: Reduction of Urinary Oxalate by Enzymatic Reduction of Dietary and Endogenous Oxalate

Paris, France (UroToday.com) Hyperoxaluria is an important etiology of urinary stone disease that is often not easily treated by dietary modifications alone, as it is also produced endogenously in the gut. Oxalate decarboxylase is an enzyme that degrades oxalate, which is why Dr. Bird and her colleagues at the University of Florida sought to harness this oxalate-reducing activity by creating an orally-administered recombinant version of oxalate decarboxylase dubbed, A0. A0 is derived from Agrocybe aegerita and is designed to function at the different pH ranges along the length of the GI tract, thus degrading dietary oxalate in the stomach, and endogenously produced oxalate found more distal in the intestines.

The investigators conducted this study using porcine subjects in a crossover study format as depicted in the image below. Eight male pigs each received a high oxalate diet (HOD), a low-oxalate diet (LOD), a HOD + A0 diet, and LOD + A0 diet, and a LOD + hydroxyproline (HP) diet with intervening washout periods. Urinary oxalate levels were measured by 24-hour total collection during the study period. 

UroToday WCE2018 Reduction of Urinary Oxalate by Enzymatic Reduction of Dietary and Endogenous Oxalate

The results showed that A0 did, in fact, reduce urinary oxalate levels both during the HOD period (71% reduction) as well as the LOD period (45% reduction). The reduction in urinary oxalate during both phases of the study indicates that A0 is effective in reducing both dietary (demonstrated during HOD) and endogenous (demonstrated during LOD) oxalate. Notably, the pigs did not experience any adverse effects from the A0.

Dr. Bird’s work demonstrates an important concept of enzyme kinetics, as she noted that there was a larger decrease in urine oxalate during the HOD phase because the A0 enzyme had a greater amount of substrate with which to interact. However, she also mentioned that continuing to increase the concentration of A0 will have little benefit to a certain extent, as all substrate (oxalate) will eventually become bound by the enzyme.

Presented by: 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, Gainesville, Florida

Co-Authors: Meekah Chaderton, Meekah Chaderton, Ming Yang, Qing-Shan Li, Haifen Liu, Aaron Cowley

Author Affiliation: University of Florida College of Medicine and College of Engineering, Gainesville, Florida, USA 

Written by: Frank Jefferson, Department of Urology, University of California-Irvine, medical writer for UroToday.com at the 36th World Congress of Endourology (WCE) and SWL - September 20-23, 2018 Paris, France