Gut Based Uremia Therapy: Simultaneously Eliminate Urea, Creatinine and Uric Acid

Eli A. Friedman¹,Anthony Macherone², Natarajan Ranganathan², Raj Mehta³, and Beena Patel³ ¹Medical Center, Brooklyn, NY; ²Kibow Biotech Inc., Philadelphia, PA.; ³Organica Inc., Valley Forge, PA
Journal of the American Society of Nephrology 12: Sept 2001 pp. 71A-72A SU-1-0520 (PS)

The quest for gut-based uremia treatment for ESRD without dialytic regimens has evaluated oral sorbents including oxidized starch, charcoal and synthetic polymers. We have devised a sorbent regimen adding probiotic urease secreting bacteria to locust bean gum and activated charcoal and report in vitro feasibility studies. Lactobacillus sporogenes (LS), Lactobacillus acidophilus (LA), Bacillus pasteurii (BP) and Escherichia coli DH5 (EC) were evaluated in the native state and as alginate-poly-L-lysine-alginate microcapsules for their ability to eliminate nitrogenous waste from artificial intestinal fluid (AIF) containing 100/150mg/dL urea, 15/30mg/dL creatinine and 15/30mg/dL uric acid in aqueous pancreatin, KH2PO4 and NaOH were in a concentration of 25mM and 20mM respectively. Activated charcoal was added to remove creatinine and uric acid while locust bean gum was included for its uric acid and creatinine sorbent capacity and water uptake.

Each bacterium, activated charcoal and locust bean gum were studied individually and added to 50mL AIF and incubated at 370C and 100rpm. Alginate-poly-L-lysine-alginate microcapsules containing BP or EC were added to normalize the protein content of the cells (~2 grams BP microcapsules and ~3 gram EC microcapsules). Aliquots were taken at 1,2,3,4,6 and 24 hours and valuated for reduction in urea nitrogen, uric acid, creatinine and formation of ammonia. In four hours, native BP removed >90% of urea while EC lowered urea by 50%. All tested bacteria completely removed urea in less than 24 hours and all produced an measurable ammonia. Concentrations of uric acid creatinine were decreased by >85%) by 1 gram of activated charcoal in about one hour. Locust bean gum was ineffective as a nitrogen binder in this system. We will now test this combination of sorbents and bacteria in animal, models of kidney failure.