Oral Probiotic Treatment for Uremia in a Porcine Model of Chronic Renal Failure
Lynn R. Willis*1, Rajash K. Handa1, Ryan F. Paterson2, Samuel C. Kim2, William W. Tinmouth2, B. Patel3, R. Dheer3, B. Pechenyak3, Pari Ranganathan3 and Natarajan Ranganathan*3.
1Department of Pharmacology and Toxicology, Indiana University School of Medicine; 2Methodist Institute for Kidney Stone Disease, Indianapolis, Indiana, and 3Kibow Biotech, Inc. Philadelphia, Pennsylvania.
Journal of the American Society of Nephrology 15: Oct 2004 pp. 700A SU-PO771
We have tested a novel oral treatment for uremia in a 5/6-nephrectomy model of chronic renal failure in miniature swine. Four male Gottingen minipigs were anesthetized and subjected to 5/6 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 with a gelatin-encapsulated formula of adsorbents and non-pathogenic bacteria for 3-4 weeks reduced Cr to 2.26±0.95 mg/dl (P<0.05). Cr had returned to baseline (2.84±1.23 mg/dl) within a month after stoppage of treatment. Neither BUN nor Hct were significantly affected during the treatment and post-treatment periods.On the last day of the protocol, the pigs were anesthetized and the remnant kidneys were perfused in situ and removed for weighing and histological analysis. The final mean weight of the remnants was 38.0±13.0 g, 3-fold greater than the mean estimated weight of the remnants immediately after surgery (13.8±4.39 g), and 53.1±11.2% of the pre-surgical total renal mass. Oral treatment with a probiotic formulation effectively and significantly reduced plasma creatinine concentration by 22.5±8.5% in a stable porcine model of chronic renal failure. Small sample size may have prevented detection of corresponding reductions in BUN and elevation of hematocrit. The model appears to hold promise for testing subsequent treatments for uremia.