Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure
CRRT in acute liver failure trial design and results
Design
Multicentre retrospective cohort analysis of a prospective registry
Treatment
Continuous renal replacement therapy
Control
Intermittent renal replacement therapy, or none
Population
1186 patients with acute liver failure in the US Acute Liver Failure Study Group registry, of whom 340 with serial ammonia measurements contributed the ammonia analysis
Follow-up
21 days
Primary endpoint
Serum ammonia and 21-day transplant-free survival
Result
From days 1 to 3, median ammonia fell by 38% with continuous renal replacement therapy, 23% with intermittent therapy and 19% with none. Against no therapy, the reduction was significant for continuous treatment (p=0.007) but not intermittent (p=0.75). After adjustment for year of enrolment, age, aetiology and disease severity, continuous therapy was associated with reduced 21-day transplant-free mortality (odds ratio 0.47, 95% CI 0.26 to 0.82) while intermittent therapy was associated with an increase (odds ratio 1.68, 95% CI 1.04 to 2.72).
Secondary endpoints
Ammonia clearance, grade of hepatic encephalopathy
In a large cohort of ALF patients, hyperammonemia was associated with high-grade HE and worse 21-day TFS. CRRT was associated with a reduction in serum ammonia level and improvement of 21-day TFS.
The trial authors, in the published abstract
How it has aged
The divergence between continuous and intermittent therapy is the interesting part, and it is biologically coherent: ammonia rebounds between intermittent sessions. Registry data with multivariable adjustment, so confounding by indication remains the obvious objection — and the mirror-image result for intermittent therapy is as easily explained by which patients get which modality as by ammonia kinetics.
Publications
Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure
Cardoso FS, Gottfried M, Tujios S, et al. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology 2018 Feb;67(2):711-720.
Ammonia fell 38% with continuous therapy versus 19% with none
Adjusted odds ratio 0.47 for 21-day transplant-free mortality with continuous therapy
Intermittent therapy associated with increased mortality, odds ratio 1.68