The Bioartificial Kidney in the Treatment of Acute Kidney Injury

Abstract

Acute kidney injury (AKI) continues to have an exceedingly high mortality rate, despite advances in dialysis technology. Current dialysis therapies replace only the filtration function of the kidney, not the critical transport, metabolic, and endocrine functions of renal tubule cells. Replacement of these additional functions would provide more complete AKI therapy and thereby change the natural history of this disease process. A renal tubule assist device (RAD) containing living renal proximal tubule cells has been successfully engineered and has demonstrated differentiated absorptive, metabolic, and endocrine functions of normal kidney in vitro and ex vivo in animal experiments. The addition of the RAD containing human cells to conventional continuous renal replacement therapy has been shown in preclinical and clinical studies to have the potential to advance AKI treatment, from enhancing renal clearance to providing more complete renal replacement therapy. This "bioartificial kidney" demonstrates metabolic activity with systemic effects and improvement of survival in patients with AKI and multiorgan failure. It also appears to influence systemic leukocyte activation and the balance of inflammatory cytokines, suggesting that cell therapy by use of the RAD may improve morbidity and mortality by altering the proinflammatory state of patients with renal failure. In addition to providing cellular metabolic function, technologies directed toward disrupting systemic inflammatory response may well enhance the clinical outcome of critically ill patients in the future. Innovative approaches to intensive renal care such as the RAD may break the mold of current institutional dialysis therapies and provide numerous opportunities to develop lifesaving technologies.