Research into the development of a wearable bioartificial kidney with a continuous hemofilter and a bioartificial tubule device using tubular epithelial cells

Current hemodialysis treatment is insufficient because of intermittent treatment and loss of tubular function. In order to overcome the loss of tubular function, a bioartificial kidney has been developed consisting of continuous hemofiltration (CHF) with 10 L/day of filtrate and a bioartificial tubule device using proximal tubular epithelial cells and hollow fiber membranes. Ten L/day of CHF enabled plasma levels of urea, creatinine, uric acid and, beta2-microglobulin in eight renal failure patients to be maintained at remarkably low levels. The concept was tested with 6 L (4 mL/min) of 10 L/day (7 mL/min) filtrate regenerated by a bioartificial tubule device and 4 L/day (3 mL/min) replaced by food and drinks. Lewis lung cancer-porcine kidney 1 (LLC-PK1) cells with a cell density of 107 cells/mL were seeded inside polysulfone hollow fiber modules four times at 1 h intervals while rotating the module 90 degrees each time, and were cultured for 48 h to form confluent monolayers. The leak rates of urea and creatinine across LLC-PK1 cell-attached polysulfone membrane modules (membrane areas: 56 cm2 and 4000 cm2) were investigated. Via conversion from 56 m2 to 1 m2 hollow fiber modules with LLC-PK1 cells for 24 h, the transport rates of H2O, glucose and Na+ were, respectively, 40, 65 and 35% of the target transported amounts from 6 L/day of filtrate. The rates are expected to approach 100% when 4-5 g/dL of albumin is added to the basal portion of the medium since the results were obtained without the addition of albumin for colloidal osmotic pressure.