Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure

Abstract

Objective: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. Design: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. Setting: All liver transplant ICUs across Australia and New Zealand. Participants: Sixty-two patients with ALF. Main outcome measures: Impact of CRRT on hyperammonaemia and patient outcomes. Results: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 mol/L (interquartile range [IQR], 91–172), median creatinine was 165 mol/L (IQR, 92–263) and median urea was 6.9 mmol/L (IQR, 3.1–12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2–12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 mol/L [IQR, 102–198] v 91 mol/L [IQR, 54–115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 mol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). Conclusion: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.

Astragaloside IV improves the pharmacokinetics of febuxostat in rats with hyperuricemic nephropathy by regulating urea metabolism in gut microbiota

“…As a result, AST reduced the abnormal increase in ammonia in the blood and faeces of HN rats. Hyperammonemia has been reported to cause tubular dilation and tubulointerstitial nephritis in mice, leading to stage 3 acute kidney injury in patients ( Warrillow et al, 2020 ). Therefore, AST could prevent hyperuricemia-induced renal injury by reducing urease activity in the gut microbiota.…”

Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center

“…Indeed, prognosis of these patients is highly variable although liver transplantation has improved overall survival in acute liver failure patients [ 35 ]. In ALF patients, other extracorporeal therapies have been put forward such as high volume plasma exchange [ 36 ] or high dose continuous renal replacement therapy (CRRT) [ 37 , 38 ]. CRRT could have a beneficial impact on hyperammonemia and consequently could lead to an improvement in transplantation free survival.…”

Ammonia and nutritional therapy in the critically ill: when to worry, when to test and how to treat?

“…The correlation between plasma ammonia concentration and the severity of encephalopathy and cerebral oedema is somewhat variable, levels of more than 100 μmol/l are highly predictive of encephalopathy in hepatic hyperammonaemia, while ammonia concentrations of more than 150 μmol/l in adults are associated with intracranial hypertension that may be complicated by neurological injury and death from brainstem herniation [1]. CRRT can successfully treat hyperammonemia-associated acute liver failure [37 ▪ ] and prevent both cerebral oedema and death in patients with urea cycle disorders [38].…”