Mode of Delivery and Dosage

We have been exploring a cocktail formulation of friendly microbes (known as probiotics) for uremia therapy applications. In continuation of our in vitro R&D published earlier (2003 ASN meeting), we have tested several oral probiotic formulations delivered in two different formats: admixed with a food ball or in a Gel Cap with variable dosages. These were tested in a limited number of 5/6th nephrectomized chronic renal failure model miniature swine. The development of this model is being independently reported by our collaborator L.R. Willis, Indiana University. Gottingen minipigs were anesthetized and subjected to 5/6th nephrectomy (open flank incisions, unilateral nephrectomy and removal of both poles of the contralateral kidney). Baseline (pre-surgery) values for plasma creatinine (Cr), BUN and hematocrit (Hct) were: 0.64±SD 0.15 mg/dl, 6.5±3.2 mg/dl, and 43.8±0.29% respectively.

Three weeks later these values were stable at Cr: 2.9±1.0 mg/dl, BUN: 53.4±22.2 mg/dl, and Hct: 32.4±5.4%.Daily oral treatment of periodically increasing dosage of selected probiotic formulations either mixed in with a food ball or gelatin-encapsulated were administered for a period of 30 to 90 days. The probiotics were chosen from among specially screened microbial strains (L.acidophilus, Bifidobacteria, L.bulgaricus, L.sporogenes, S.thermophilus and B.pasteurii.), and included in varied microbial counts (CFU/g). Periodic physical examinations, blood draw, and biochemical analysis were performed during the period of investigation. No significant changes were found in the case of the oral treatment with a food ball containing low dosage of total bacteria (less than 1010 CFU/g). Oral treatment with our formulation #5, delivered as a gel cap containing high bacterial count (1011 CFU/g), effectively and significantly reduced plasma creatinine by 22.5 ±8.5% in stable CRF swines. Further investigations with a larger number of animals and evaluation of additional biochemical parameters are warranted.