Presentation Authors: Emily Quintero*, Gainesville, FL, Sabrina Buzzard, High Springs, FL, Alan Ryan, Boynton Beach , FL, Gary Stevens, Bastrop, TX, Ira Klimberg, Englewood, FL, Victoria Bird, Gainesville, FL
Introduction: Hyperoxaluria is common in calcium oxalate kidney stone formers and is typically associated with excessive intake of dietary oxalate or increased endogenous production. Oral oxalate-reducing enzymes break down dietary oxalate in the gastrointestinal tract resulting in reduced urinary oxalate. Objective: To explore an acid stable OxDC as a means to reduce urinary oxalate.
Methods: This was a prospective, double-blind, randomized, placebo-controlled, cross-over study that evaluated an orally administered OxDC in normal healthy volunteers with BMI of 18.5â€“29.9 kg/m2, and urinary oxalate (UOx) < 40.5mg/24 hours. Subjects were randomized to 2 different cross-over sequences separated by a washout period of 2 days. A controlled diet (750-800 mg oxalate, 500-550 mg calcium per day) was utilized and six 24-hour UOx were measured. Subjects were given approximately 1000 units (ïmol/min/mg) of enzyme or representative placebo with meals 3 times per day over 4 treatment days.
Results: Thirty-three healthy subjects (16 female, 17 male) with a mean age of 36.2 years (range 19-53 years) completed the study. The mean eGFR and BMI were 96.8 (SD 18) and 24.7 (SD 3.1), respectively. On controlled diet, and controlled diet with placebo, mean urinary oxalate was approximately 43mg/24h and 40mg/24h, respectively. On treatment, average urinary oxalate was significantly reduced to approximately 30mg/24h. Preliminary data analysis indicates that there were no significant differences in any of the other urinary parameters measured (Ca, Cr, Mg, Cit, Uric). Reduction was seen in 31/33 subjects (94%). Baseline corrected within-subject mean difference in 24h UOx between treatment groups was 12.6mg or 30% (p < 0.0001). There were no serious adverse events (AEs). All AEs were mild-moderate. There were no treatment related AEs. No subjects discontinued study treatment.
Conclusions: Oxalate decarboxylase is an orally administered oxalate reducing enzyme capable of significantly reducing UOx levels without having an effect on creatinine clearance, urine creatinine or other solutes related to supersaturation of calcium oxalate.
Source of Funding: National Institutes of Health