Expanding the Boundaries of Combined Renal Replacement Therapy for Non-Renal Indications

Over the last decades, there have been major advancements in the field of renal replacement therapy (RRT) with utilization of newer technologies and advent of various modalities. Once exclusively used for treatment of renal failure and its metabolic consequences, the science of RRT has expanded to include non-renal indications such as treatment of fluid overload in patients with refractory heart failure. Hepatic encephalopathy due to sudden rise in serum ammonia level in the setting of acute liver failure represents an underexplored area in which RRT can potentially be helpful. While the key role of hyperammonemia in the pathogenesis of hepatic encephalopathy in patients with liver failure is well established, emerging data points to distinct pathophysiologic mechanisms underlying chronic alterations in neural metabolic functions and acute changes in cerebral perfusion. In the acute setting, ammonia can cross the blood-brain barrier at high levels leading to sudden formation of strong osmolytes, significant transcellular shift of water, and cerebral edema. Herein, we provide a brief overview of the role of RRT in management of acute hyperammonemia in the setting of acute liver failure and discuss the practical aspects of the available therapeutic modalities. Larger studies are needed to shed light on a number of clinical aspects such as the impact on the outcomes, criteria for selection of the patients that would benefit most from this therapeutic approach, optimal timing of initiation of RRT, and the most appropriate modality.