Supplementary Material for: Endotoxemia Correlates with Kidney Function and Length of Stay in Critically Ill Patients

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. Pre-clinical 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 hours 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 day 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 non-responders (NR); and (2) used as a continuous variable. Results: Patients with EAA 0.6 had a higher prevalence of proteinuria, and lower SaO2/FiO2 ratio versus patients with EAA <0.6. EAA levels positively correlated with 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.