Current renal substitution therapy with hemodialysis or hemofiltration has
been the only successful long-term ex vivo organ substitution therapy to da
te. Although this approach is life sustaining, it is still unacceptably sub
optimal with poor clinical outcomes of patients with either chronic end-sta
ge renal disease or acute renal failure. This current therapy utilizes synt
hetic membranes to substitute for the small solute clearance function of th
e renal glomerulus but does not replace the transport, metabolic, and endoc
rinologic functions of the tubular cells. The addition of tubule cell repla
cement therapy in a tissue-engineered bioartificial kidney comprising both
biologic and synthetic components will likely optimize renal replacement to
improve clinical outcomes. This report demonstrates that the combination o
f a synthetic hemofiltration device and a renal tubule cell therapy device
containing porcine renal tubule cells in an extracorporeal perfusion circui
t successfully replaces filtration, transport, metabolic, and endocrinologi
c functions of the kidney in acutely uremic dogs.