S1001 Anti-High Mobility Group Box Chromosomal Protein 1 Antibodies Improve Survival of Rats with Fulminant Hepatic Failure

Abstract

Background: Kidney injury has been recognized in association with acetaminophen (APAP) toxicity but not well characterized. The incidence and consequences of acute kidney injury (AKI) in acute liver failure (ALF) are unknown. Aim: Determine the incidence and outcomes of AKI in APAP ALF. Methods: Between 1998 and 2008, 1349 patients were enrolled at 23 ALF Study Group sites across the US using standard ALF criteria. We examined this database for AKI as defined by modified RIFLE criteria (Crit Care 2007; 11:R31) using the ratio of max and admission creatinine (Cr). The frequency of AKI in APAP ALF was compared to other causes of ALF. We considered shock separately since AKI would be expected in the setting of ischemia. Patients were grouped by etiology and degree of renal impairment. AKI ranged from none (Cr ≤ 1.3 mg/dL) to need for renal replacement therapy (RRT). Multivariate analysis was performed for associations for AKI across groups.Results: Incidence of any AKI in APAP ALF was 73% compared to 66% in other ALF (p<0.05). AKI in APAP tended to be more severe with 34% requiring RRT compared to 25% in other etiologies (p<0.001). The median max Cr was higher for APAP ALF across all AKI stages (2.2-6.1 mg/ dL) compared to the others (2.1-4.5 mg/dL). APAP ALF patients were younger [37 (1878)], mostly female (81%), and had concomitant alcohol use (51%). Neither gender, age, nor alcohol use appeared to influence the frequency of AKI in APAP. There was no relation to dose ingested or degree of ALT elevation. In APAP and shock AKI, coma grade and INR were higher than no AKI but this was not seen in the others. Across all groups the need for RRT negatively impacted spontaneous survival (p<0.001). Despite higher incidence of AKI in APAP and shock, spontaneous survival was significantly better than in other ALF (RRT 53%, 59%, 17% p<0.05; overall 73%, 72%, 31% p<0.05).Conclusions: Incidence of AKI in APAP ALF is high and appears to be independent of dose, age, gender and degree of liver injury. Over 30% required renal replacement. Despite the severity of AKI, APAP ALF, like shock, still had an overall favorable prognosis suggesting a transient renal insult. The mechanism of APAP AKI probably differs from that of APAP liver injury and merits further investigation.