Renal cell therapy and beyond

Although current dialysis techniques have transformed acute and chronic renal failure from uniformly fatal clinical disorders into treatable diseases, these therapies replace only the water and solute clearance function of the kidney and have reached a point where little further therapeutic improvement can be anticipated. In addition to their metabolic and endocrine functions, renal tubule cells presumably play an important role in the systemic inflammatory balance by participating in the complex and dynamic network of leukocyte action and pro- and anti-inflammatory cytokines. Loss of this function may result in a propensity to develop systemic inflammatory response syndrome (SIRS), multiorgan dysfunction, and a high risk of death in acute kidney injury (AKI), and may relate to chronic inflammatory state in end-stage renal disease (ESRD). A renal tubule cell assist device (RAD) containing animal or human renal tubule cells has been recently developed with the purpose of integrating the functions of tubule cells with the filtration function of current dialysis to offer a more complete renal replacement therapy. The viability and functionality of this device were confirmed in in vitro experiments and large animal studies, and recently the RAD's clinical therapeutic benefit was demonstrated with a series of FDA-approved human trials. Another novel synthetic membrane extracorporeal device that binds and inhibits circulating leukocytes has been developed with the purpose of reducing microvascular damage promoted primarily via activated circulating leukocytes in AKI and SIRS. This device, called a selective cytopheretic inhibitory device, mimics immunomodulation and duplicates RAD efficiency in preliminary studies. Both devices may become comprehensive treatments, replacing full renal function and correcting inflammatory imbalance in patients with acute and chronic renal disorders.