Bioartificial kidney in the treatment of acute renal failure associated with sepsis

Abstract

Acute renal failure (ARF) associated with sepsis has a high rate of mortality. It is not merely a surrogate marker for severity of disease but also an independent predictor of mortality and a separate pathogenic entity, even when nearly physiological doses of fluid and small-molecule clearance are maintained with currently available renal replacement therapies (RRT).The techniques to remove cytokines, including high-volume haemofiltration, haemodialysis using high-cut-off haemofilters, and absorptive techniques, lead to some improvement in outcome but are still insufficient to reverse the complicated biological dysregulation resulting from ARF associated with sepsis. The novel and exciting technique of cell therapy, which is based on the principle of using functional cells to replace a greater range of renal functions, may add significant benefit to current RRT in dealing with this disease process. Because renal tubule cells appear to play critical roles in immunoregulation, renal tubule cell therapy during ARF associated with sepsis should alter the detrimental multiple-organ consequences of sepsis. The development of a bioartificial kidney consisting of a conventional haemofiltration cartridge in series with a renal tubule assist device containing renal proximal tubule cells represents a new therapeutic approach to this clinical disorder. The results to date of large animal studies and recent Phase I/II and Phase II clinical trials show that such a device replaces multiple kidney functions and modifies the sepsis condition to improve survival in ARF. © 2006 The Authors.