Cell therapy in kidney failure

Abstract

Current therapy for acute renal failure continues to have an exceedingly high mortality rate, exceeding 50% even with dialytic or hemofiltrative support. Current renal replacement therapy in ARF only substitutes for filtration function of the kidney but not its cellular metabolic functions. Replacing these metabolic functions may optimize current therapy for this devastating disease process. In this regard, a renal tubule assist device (RAD) has been developed to be placed in an extracorporeal continuous hemoperfusion circuit in series with a hemofilter. The RAD consists of porcine renal proximal tubule cells grown as confluent monolayers in a multifiber bioreactor with a membrane surface area from 0.4 to 1.6 m2. The cells along the inner surface of the hollow fibers are immunoprotected from the patient's blood by the hollow fiber membrane. In vitro experiments demonstrate that this device possesses differentiated renal transport, metabolic and endocrinologic properties. These properties, in fact, are responsive to normal physiological regulatory parameters. In preliminary experiments in uremic dogs, this device has also been shown to tolerate a uremic environment while providing reabsorptive, metabolic, and endocrinologic activity. Pilot human trials of the RAD are anticipated within the next year to improve current renal replacement therapy in this devastating disease process.