Dataset Information

Outcomes of renal dysfunction in patients with acute liver failure.

ABSTRACT:

Background

Although acute kidney injury (AKI) often accompanies acute liver failure (ALF), its impact on long-term outcome is unknown.

Objective

This study examines the incidence, severity and outcomes of AKI in patients with ALF.

Methods

A total of 134 ALF patients treated at Hannover Medical School between 1995 and 2013 were retrospectively analyzed.

Results

Fifty-four ALF patients (40.3%) demonstrated AKI, as defined by the acute kidney injury network (AKIN) classification, on intensive care unit (ICU) admission, and 85 patients (63.4%) developed AKI prior to ALF recovery, emergency liver transplantation (ELT) or death. AKI severity was closely associated with other end-organ damage (p?p?=?0.003). One-hundred-and-three (76.9%) patients reached the combined endpoint of ELT or death, and 42 (31.3%) patients died within 28 days. AKIN stage 3 at ICU admission was the strongest independent predictor of 28-day overall mortality (hazard ratio 3.48, 95% confidence interval 1.75-6.93, p?p?ConclusionsAKI is a frequent complication in ALF that correlates with remote organ damage and long-term creatinine levels and independently predicts outcome.

SUBMITTER: Hadem J

PROVIDER: S-EPMC6466757 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Outcomes of renal dysfunction in patients with acute liver failure.

Hadem Johannes J Kielstein Jan T JT Manns Michael P MP Kümpers Philipp P Lukasz Alexander A

United European gastroenterology journal 20181203 3

<h4>Background</h4>Although acute kidney injury (AKI) often accompanies acute liver failure (ALF), its impact on long-term outcome is unknown.<h4>Objective</h4>This study examines the incidence, severity and outcomes of AKI in patients with ALF.<h4>Methods</h4>A total of 134 ALF patients treated at Hannover Medical School between 1995 and 2013 were retrospectively analyzed.<h4>Results</h4>Fifty-four ALF patients (40.3%) demonstrated AKI, as defined by the acute kidney injury network (AKIN) class ...[more]

PMID: 31019707

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Project description:Background and objectivesThe relationship among anemia, renal dysfunction, left ventricular ejection fraction, and outcomes of patients hospitalized for acute decompensated heart failure is unclear. The aim of this study was to evaluate the association between cardiorenal anemia syndrome and postdischarge outcomes in patients hospitalized for heart failure with a preserved or reduced ejection fraction.Design, setting, participants, & measurementsOf 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry between April 1, 2007 and December 31, 2011, 4393 patients were evaluated to investigate the association among anemia, renal dysfunction, preserved or reduced ejection fraction, and the primary end point (mortality and readmission for heart failure since discharge). The patients were divided into four groups on the basis of eGFR and hemoglobin at discharge. The median follow-up period after discharge was 432 (range=253-659) days.ResultsThe primary end point was reached in 37.6% and 34.8% of the preserved and reduced ejection fraction groups, respectively. After adjustment for multiple comorbidities, there was no significant association of either renal dysfunction or anemia alone with the primary end point in patients with preserved ejection fraction, but the combination of renal dysfunction and anemia was associated with a significantly higher risk than that without either condition (hazard ratio, 1.54; 95% confidence interval, 1.12 to 2.12; P<0.01). In patients with reduced ejection fraction, adjusted analysis showed that a significantly higher risk of the primary end point was associated with renal dysfunction alone (hazard ratio, 1.65; 95% confidence interval, 1.21 to 2.25; P=0.002) and also, renal dysfunction plus anemia relative to the risk without either condition (hazard ratio, 2.19; 95% confidence interval, 1.62 to 2.96; P<0.001).ConclusionsThe findings show that renal dysfunction combined with anemia is associated with an increased risk of adverse postdischarge outcomes in patients with preserved ejection fraction, whereas renal dysfunction is an independent predictor of the risk of adverse outcomes in patients with reduced ejection fraction, regardless of anemia.

Project description:Background&aims: Patients with acute decompensation (AD) of cirrhosis progressing to acute-on-chronic liver failure (ACLF) present a systemic hyperinflammatory response associated with increased circulating levels of small-molecule metabolites. To investigate whether these alterations reflect inadequate cell energy output, we assessed mitochondrial morphology and central metabolic pathways with emphasis on the tricarboxylic acid (TCA) cycle in peripheral leukocytes from AD patients with and without ACLF. Methods: The study included samples from AD patients (102 without and 126 with ACLF) along with 41 healthy subjects. Leukocyte mitochondria ultrastructure was visualized by transmission electron microscopy and cytosolic and mitochondrial metabolic fluxes were determined by assessing NADH/FADH 2 production from various substrates. Plasma GDF15 and FGF21 were determined by Luminex and acylcarnitines by LC-MS/MS. Gene expression was analyzed by RNA-seq and PCR-based glucose metabolism profiler array. Results: Mitochondrial ultrastructure in patients with advanced cirrhosis was distinguished by cristae rarefication and swelling. The number of mitochondria per leukocyte was higher in patients, accompanied by a reduction in their size. Increased FGF21 and C:6- and C:8-carnitines predicted mortality whereas GDF15 strongly correlated with a gene set signature related to leukocyte activation. Metabolic flux analyses revealed increased energy production in mononuclear leukocytes from patients with preferential involvement of extra-mitochondrial pathways, supported by upregulated expression of genes encoding enzymes of the glycolytic and pentose phosphate pathways. In ACLF patients, mitochondrial function analysis uncovered two break-points in the TCA cycle at the isocitrate dehydrogenase and succinate dehydrogenase level, which were bridged by anaplerotic reactions involving glutaminolysis and nucleoside metabolism. Conclusions: Our findings provide evidence at the cellular, organelle and biochemical levels that severe mitochondrial dysfunction governs immunometabolism in leukocytes from patients with AD cirrhosis and ACLF.

Project description:Background & aimsPatients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF.MethodsSerum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices.ResultsComa grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF.ConclusionsThe ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD.

Dataset Information

Outcomes of renal dysfunction in patients with acute liver failure.

Background

Objective

Methods

Results

Publications

Outcomes of renal dysfunction in patients with acute liver failure.

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