Substitution of the Kidney Function by the Bowel in Azotemia

B G Patel Ph.D. 1*, N Ranganathan Ph.D. 1, O A Zelenaia Ph.D. 1, R S Dheer B.S. 1, W Verstraete Ph.D. 2, T Van de Wiele Ph.D. 2 and E A Friedman M.D. 3
1 R&D Microbiology, Kibow Biotech Inc., Philadelphia, PA, United States, 2 Laboratory Microbial Ecology and Technology, Fac Agricultural and Applied Biological Sciences, Gent, Belgium, 3 Department of Medicine, SUNY Brooklyn Health Science Center, New York, NY, United States.
Journal of the American Society of Nephrology 15: Oct 2004 pp. 700A SU-PO771

Chronic Kidney Disease (CKD) is characterized by reduced kidney function between 50 to 85%. It is a widely spread disease affecting more than 200 millions patients worldwide. These CKD patients demonstrate elevated blood levels of uremic metabolites due to decreased ability of their kidneys to filter these uremic metabolites. The increased concentration of uremic metabolites such as urea and creatinine and possibly other waste products circulating in blood promotes a passive diffusion across the intestinal cell wall and thus permeates into the large bowel or gut. The bowel represents a complex ecosystem in which a delicate balance exists between intestinal micro flora and host. Bacterial concentration ranges between 1011 to 1012 cfu per gram of colonic content. We developed an orally ingestible probiotic microbial formulation in which a specific strain of microbe consumes the commonly recognized surrogate uremic toxins – urea.

S. thermophilus is a gram positive non-motile and non-spore forming rods nonindigenous to the intestinal track of infants, adults, and various animals. S. thermophilus is urealytic and generally used along with Lactobacillus spp as a starter culture for manufacturer of several fermented dairy food including yogurt and cheese. The specifically chosen strain in our in-vitro study showed only a one log cfu loss from 109 cfu after passing through gastric and bile juices. This strain showed not only good survivability but also ability to proliferate and hydrolyze urea (100 to230mg/dl in 18hr).

In the present study utilizing the Simulated Human Intestinal Microbial Ecosystem (SHIME), we investigated the ability of our S. thermophilus KB19 strain to consume mainly urea in an environment mimicking the CKD status in the large gastrointestinal track. Supplementation of 11 log cfu of freeze dried S. thermophilus to the SHIME reactor showed a substantial amount of urea utilization in a complex microbial feed suspension. Significant decrease in urea and creatinine was also observed in ascending and descending colon respectively from (6.9±0.48 to 4.6±0.83; 191.0±13.0 to 150±17.2 mg/dl, p<0.01) compared to high uremic period.