Development of bioartificial kidneys.

Bioartificial kidneys, which consist of continuous haemofiltration and bioartificial tubules using tubular epithelial cells, have been studied since 1987. The bioartificial tubules consist of hollow fibre modules and tubular epithelial cells grown on the hollow fibre membranes after coating with extracellular matrices. The kinds of tubular epithelial cells, extracellular matrices and artificial membranes therefore have been investigated and then the most appropriate cell and materials have been selected on the basis of the development of bioartificial kidneys. Successful seeding to form confluent monolayers on the surfaces of hollow fibers is not easy, but this method has already been established. Renal assist devices using human renal proximal tubular epithelial cells have been used in the treatment of acute renal failure patients with endotoxemia by Humes et al., and successful treatment of acute renal failure patients with these devices was reported in 2001 and 2002, in which the improved mortality rate of those patients was shown. A bioartificial kidney, in which cDNA of multidrug resistance protein-1 was transfected into tubular epithelial cells that were then grown on the outer surfaces of hollow fibers, was used in the experimental treatment of digoxin-intoxicated dogs. Rapidly reduced digoxin levels were noted in the plasma of the dogs after treatment. Bioartificial kidneys, however, have never been used in the long-term treatment of a maintenance dialysis patient, although patients need those kidneys. In order to establish long-term treatment with a bioartificial kidney, each haemofilter has to function for more than one week without systemic anticoagulation and a bioartificial tubule must function for 3-4 weeks.