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

Abstract

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.

Role of RRT in Adult Patients with Hyperammonemia

“…In patients with chronic liver disease; the rise in serum ammonia is slow and gradual [19]. As mentioned before, this slow rise will allow for compensatory mechanisms to decrease the osmolarity, and also for compensatory increase in the ammonia metabolism by other organs [5,8,19].…”

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A

“…Ammonia is a major regulator of acid-based homeostasis (13), and extracellular pH and plasma potassium concentration play an important role in the regulation of ammonia synthesis and transport (13). Hypokalemia can precipitate encephalopathy by stimulating ammonia-genesis in the tubule ( 14) and bicarbonate-containing fluids induce cerebral vasodilation, facilitate ammonia entry in the brain, and thereby lead to intracranial hypertension (15).…”

“…Ammonia is a 17 g/mol non-protein-bound element with a diffusive clearance similar to urea; both continuous and intermittent modalities of RRT are efficient to remove it from the plasma but with different rates (13,15). The timing to start dialysis in adults with ALF, hyperammonemia, and cerebral edema is still unknown (13,15). Some references recommend dialysis when ammonia levels approach 200 micromol/L (16).…”

“…It has been suggested to consider it when the ammonia level is three times more than the upper limit of normal or when patients are severely encephalopathic, even before the advancement of AKI (13). Continuous RRT (CRRT) used alone or with intermittent hemodialysis is considered the method of choice because it provides uninterrupted clearance for ammonia reducing post-hemodialysis rebound caused by a deferred ammonia shift from extravascular compartments (13,15). It allows a gradual reduction in serum osmolality and less shift of water across the blood-brain barrier to prevent the worsening of cerebral edema in patients with high ICP.…”

“…It allows a gradual reduction in serum osmolality and less shift of water across the blood-brain barrier to prevent the worsening of cerebral edema in patients with high ICP. It also allows temperature control and slow correction of metabolic abnormalities such as hyponatremia (15). However, Cardoso et al demonstrated that there was no statistically significant difference in ammonia reduction between the CRRT and intermittent hemodialysis groups; however, the use of CRRT was associated with a reduction in 21-day transplant-free all-cause mortality, whereas intermittent hemodialysis was associated with an increase in mortality (17).…”