Association between Endotoxin Activity and Acute Kidney Injury in Cardiac Patients Undergoing Cardiopulmonary Bypass

Paternoster, Gianluca; Rubino, Gianni; Balducci, Antonio; Maiorano, Rosmunda; Brienza, Nicola

doi:10.1159/000356792

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Systemic hypotension, direct renal vasoconstriction, activation of vasoactive hormones, and activation of inflammatory pathways by endotoxins might all contribute to sepsis-associated AKI [ 21 ]. The release of endotoxin into the circulatory system is a well-documented phenomenon that occurs during cardiopulmonary bypass procedure and after its discontinuation [ 9 ], which likely originates from increased endothelial permeability following ischemia and reperfusion of the gut. Increased EA has been previously associated with renal dysfunction in the setting of infection and sepsis involving altered glomerular filtration, renal tubular damage, and inflammation, leading to cell apoptosis [ 21 ].…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Monti et al [ 8 ] also showed that high EA level in patients with sepsis was associated with higher vasopressor requirements and increased hospital mortality as compared with intermediate and low EA groups. While elevation in EA occurs as a result of gram-negative bacteremia, high EA levels have also been reported to occur independent of gram-negative bacteremia [ 9 , 10 ], suggesting the potential for endotoxin translocation across a dysfunctional gastrointestinal barrier. Furthermore, ischemia-mediated gut barrier dysfunction contributing to organ failure, in the absence of primary gastrointestinal injury, has been supported by experimental models [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has also been shown that adverse ventilation strategy can cause pulmonary to systemic translocation of endotoxins [ 15 ]. In addition, the inflammatory response to COVID-19 could have been augmented by a 2nd hit, such as mechanical ventilation (MV) or inflammatory response to trauma [ 9 , 10 ]. Furthermore, during the previous H1N1 and H5N1 viral pandemics, endotoxemia was reported in the absence of gram-negative bacteremia [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Endotoxemia in Critically Ill Patients with COVID-19

et al. 2021

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Introduction: Mechanism(s) mediating critical illness in coronavirus disease 2019 (COVID-19) remain unclear. Previous reports demonstrate the existence of endotoxemia in viral infections without superimposed gram-negative bacteremia, but the rate and severity of endotoxemia in critically ill patients with COVID-19 requires further exploration. Materials and Methods: This is a single-center cross-sectional study of 92 intensive care unit patients diagnosed with COVID-19 pneumonia. Endotoxin activity (EA) was measured in patients that met the following criteria: (1) age ≥18 years and (2) multi-organ dysfunction score >9 from March 24, 2020, to June 20, 2020. Results: A total of 32 patients met the inclusion/exclusion criteria for measurement of EA. The median age of the study cohort was 60 years with a majority male (21/32, 65%) with hypertension (50%). A significant proportion of the patients exhibited either elevated EA in the intermediate range (0.40–0.59 EA units) (10/32, 31%) or high range (≥0.60 EA units) (14/32, 44%) or were nonresponders (NRs, low neutrophil response) to EA (6/32, 19%), with the presence of gram-negative bacteremia only in 2/32 (6%) patients. Low EA was reported in 2/32 patients. NRs (5/6, 83%) and patients with high EA (7/14, 50%) exhibited higher acute kidney injury (AKI) as compared to patients with low/intermediate EA level (1/12, 8.3%). Discussion/Conclusion: Elevated EA was observed in a large majority of critically ill patients with COVID-19 and multi-organ dysfunction despite a low incidence of concurrent gram-negative bacteremia. While we observed that elevated EA and nonresponsiveness to EA were associated with AKI in critically ill patients with COVID-19, these findings require further validation in larger longitudinal cohorts.

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Section: Discussion/conclusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endotoxemia in Critically Ill Patients with COVID-19

et al. 2021

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“…Recent studies have shown that higher EAA levels were associated with AKI in patients with COVID-19 [16, 17]. A small study in 18 patients undergoing cardiopulmonary bypass procedure also demonstrated elevated EAA levels in patients who developed AKI versus those who did not [20]. In the current study, only 9/124 patients (7.3%) were positive for SARS-CoV-2, therefore our study is the first to show correlations between serial endotoxin levels and kidney outcomes in a broad cohort of critically ill patients.…”

Section: Discussionmentioning

confidence: 99%

Endotoxemia Correlates with Kidney Function and Length of Stay in Critically Ill Patients

Piret,

Khan,

Fairuz

et al. 2023

Blood Purif

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Introduction: Endotoxin is a key driver of sepsis, which frequently causes acute kidney injury (AKI). However, endotoxins may also be found in non-bacteremic critically ill patients, likely from intestinal translocation. Preclinical models show that endotoxins can directly injure the kidneys, and in COVID-19 patients, endotoxemia correlated with AKI. We sought to determine correlations between endotoxemia and kidney and hospital outcomes in a broad group of critically ill patients. Methods: In this single-center, serial prospective study, 124 predominantly Caucasian adult patients were recruited within 48 h of admission to Stony Brook University Hospital Intensive Care Unit (ICU). Demographics, vital signs, laboratory data, and outcomes were collected. Circulating endotoxin was measured on days 1, 4, and 8 using the endotoxin activity assay (EAA). The association of EAA with outcomes was examined with EAA: (1) categorized as <0.6, ≥0.6, and nonresponders (NRs); and (2) used as a continuous variable. Results: Patients with EAA ≥0.6 had a higher prevalence of proteinuria, and lower arterial oxygen saturation (SaO2) to fraction of inspired oxygen (FiO2) (SaO2/FiO2) ratio versus patients with EAA <0.6. EAA levels positively correlated with serum creatinine (sCr) levels on day 1. Patients whose EAA level stayed ≥0.6 had a slower decline in sCr compared to those whose EAA started at ≥0.6 and subsequently declined. Patients with AKI stage 1 and EAA ≥0.6 on day 1 showed slower decline in sCr compared to patients with stage 1 AKI and EAA <0.6. EAA ≥0.6 and NR patients had longer hospital stay and delayed ICU discharge versus EAA <0.6. Conclusions: High EAA levels correlated with worse kidney function and outcomes. Patients whose EAA levels fell, and those with AKI stage I and day 1 EAA <0.6 recovered more quickly compared to those with EAA ≥0.6, suggesting that removal of circulating endotoxins may be beneficial in critically ill patients.

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“…Additionally, we compared the APACHE II scores, SOFA scores, inotropic scores, lactate, and Cr levels, which are reported factors related to endotoxemia evaluated by EA levels. [4,7,23] NT pro-BNP [24] and procalcitonin, [25] which have been reported to be prognostic biomarkers for sepsis, were also compared. The association between variables was assessed using Wilcoxon rank sum testing and Fisher exact test.…”

Section: Methodsmentioning

confidence: 99%

Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock

Sekino

Funaoka

Sato³

et al. 2019

Medicine

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Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinical course, and other related factors. This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein (I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia, and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated. A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission. However, there was no significant correlation between EA and I-FABP levels (Spearman ρ = 0.002, P = .993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factors related to high EA levels. In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positive septic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia. Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated.

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Association between Endotoxin Activity and Acute Kidney Injury in Cardiac Patients Undergoing Cardiopulmonary Bypass

Cited by 6 publications

References 33 publications

Endotoxemia in Critically Ill Patients with COVID-19

Endotoxemia in Critically Ill Patients with COVID-19

Endotoxemia Correlates with Kidney Function and Length of Stay in Critically Ill Patients

Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock

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