Oral Bacteriotherapy Effectively Reduces Severity of Azotemia in 5/6th Nephrectomized Rats

Beena G Patel, Ph.D.¹, Olga A Zelenaia, Ph.D.¹, Rahul S Dheer, B.S.¹, Natarajan Ranganathan, Ph.D.¹, Eli A Friedman, M.D.²
¹Kibow Biotech Inc., Philadelphia, PA, ²Department of Medicine, SUNY Brooklyn Health Science Center, New York, NY.
Journal of the American Society of Nephrology 14: Nov 2003 pp. 765A SU-PO1044

We tested the hypothesis that selected bacteria instilled into the gastrointestinal tract might convert nitrogenous wastes accumulated in renal insufficiency into nontoxic compounds. In renal patients, nitrogenous solutes traverse intestinal capillaries into the bowel through diffusion. We strive to develop a clinically applicable product containing live bacteria that may consume excess urea, creatinine and “uremic” solutes. Sprague-Dawley rats weighing 281.20+/-41.6gm male/female were subjected to 5/6th nephrectomy, after measurement of baseline weight, BUN, serum creatinine, urine volume, and fecal flora composition distributed in to groups.

The study group consisted of 36 nephrectomized rats and 6 controls. After a two-week post surgery stabilization, cohorts of six rats were fed standard rat chow plus one of the following regimens: 1) placebo, 2) B. pasteurii, 3)L. sporogenes, 4) L. acidophilus, L. bulgaricus, Bifidus, S. thermophilus, L. casei, L. reuteri, 5) L. acidophilus, L. bulgaricus, Bifidus, S. thermophilus and 6) S. boulardii (strains were established and maintained by Kibow Biotech). Subsequent blood, urine, and fecese measurements were obtained every 30 days for a total of 120 days.

Subtotally nephrectomized rats fed B. pasteurii and L. sporogenes had lower BUN levels (62.0+/-21, 63.0+/-26 mg/dl) compared with placebo (99.0+/-46 mg/dl) a reduction of (38 and 37%). Serum creatinine levels were similarly reduced in rats fed with B. pasteurii and L. sporogenes (0.9+/-0.25,0.9+/-0.2mg/dl) compared to placebo (1.5+/-0.56mg/dl) a reduction of 40% in both group. Rats fed with regimens 4, 5, and 6 did not evince significant difference in BUN or serum creatinine, compared to placebo. Feeding increased the feacal count for the appropriate group of bacteria in all groups at 8 weeks. These preliminary studies indicate that bacteria previously known to metabolize urea and creatinine in vitro perform the same metabolic conversions in living partially nephrectomized rats. Whether similar activity is discerned in uremic patients and large animals is the subject of derivative study.