ABSTRACT
JILL A. O'LOUGHLIN *, JAN M. BRUDER and MICHAEL J. LYSAGHT Center for Biomedical Engineering, Brown University, Box G-B395, Providence, R! 02912-G, USA
Received 3 December 2003; accepted 15 April 2004
Abstract-This paper begins with an extensive review of previous research on the degradation of non-protein nitrogen compounds for improved therapy of renal failure. During the 1970s, Malchesky established that naturally occurring strains of microorganisms were highly effective for the in vitro degradation of urea and other compounds found in urine, and that these bacteria could be conditioned with selected media to enhance growth and degradation efficiency. A few years later, Setala introduced the concept of oral delivery of lyophilized bacteria, harvested from soil, to uremic patients, for degradation of non-protein nitrogen compounds. In the 1990s, Chang proposed delivery of encapsulated genetically modified bacteria for removal of uremic waste products in vitro and in vivo. Recently, our group has pursued the idea of orally delivering formulated combinations of enzymes or modified bacteria. A new study is also described, which characterizes the capacity of a single alginate microcapsule containing a mixture of genetically modified cells and enzyme to degrade urea, uric acid and creatinine. The combination capsules were found to be effective in vitro and in vivo in a rodent model of chemically-induced renal failure. Reduction of urea concentration in vivo required co-administration of a cation exchange resin to adsorb ammonia. Increased investigative effort is warranted for these approaches which offer significant potential as an adjunct to conventional forms of dialysis.
