Development of bio-artificial kidney

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Anionic middle molecule uremic toxins, which can not be removed by conventional hemodialysis, play major role for progress of arteriosclerosis in patients with chronic renal failure. Most of the toxins, such as indoxyl sulfate, is secreted via organic anion transporter-3 (OAT-3) in proximal tubule cells in healthy subjects. To develop a novel hybrid artificial kidney, where the proximal tubular cells over-expressing OAT-3 are cultured on hollow fibers, we performed following experiments.1) We established cultured proximal tubule cells over-expressing OAT-3. We confirmed higher transport of indoxyl sulfate in the cells and also higher expression of the protein by Western blot and immuno-histochemistry.2) We succeeded to seed the cells onto hollowfiber modules, which we previously reported.3) We found higher selective removal of indoxyl sulfate by the system in vitro. The clearance of indoxyl sulfate was 38 ml/min/m2, which was 8-times higher than that with control cells.4) We also applied this system to dogs with or without renal failure. We found high removal capacity of indoxyl sulfate from circulating blood of renal failure dog with a few adverse reactions.Thus, we succeeded to develop a novel hybrid artificial kidney with proximal tubular cells over-expressing OAT-3. This system may be useful to remove uremic toxins which can not be removed by conventional hemodialysis.