Examining Associations of Circulating Endotoxin With Nutritional Status, Inflammation, and Mortality in Hemodialysis Patients

Abstract

Objective Lipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram negative bacteria. Sub-clinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis patients. Endotoxin level and clinical effect are determined by its soluble receptor sCD14 and high density lipoprotein. We examine the hypothesis that endotoxin level correlates with mortality. Methods In this cohort study, endotoxin levels were measured in 306 long-term hemodialysis patients who were then followed for up to 42 months. Soluble CD14 and cytokines levels were also measured. Results The mean (±SD) endotoxin level was 2.31±3.10 EU/ml (min: 0.26 EU/ml, max: 22.94 EU/ml, inter-quartile range: 1.33EU/ml, median: 1.27EU/ml). Endotoxin correlated with C-reactive protein (r = 0.11, p<0.04). On multivariate logistic regression analysis, high body mass index (BMI) and low HDL cholesterol levels were associated with higher endotoxinemia (endotoxin below or above of median). In multivariable Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the 3rd quartile vs. 1st quartile was associated with a trend towards increased hazard ratio (HR) for death (HR 1.83, 95% confidence interval: 0.93–3.6, p=0.08). Conclusions In this hemodialysis cohort, we found associations between endotoxinemia and CRP, body composition and HDL. A moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to asses the effect of endotoxemia on mortality in dialysis population.

Hypertension as an autoimmune and inflammatory disease

“…Interestingly, D-lactate is a marker of intestinal wall permeability to bacteria and toxins from the gut lumen. [65][66][67] Therefore, this preliminary evidence shows that gut microbiota may be related to hypertension (Figure 2). Studies are needed to highlight the underlying mechanisms in different hypertensive species, such as Dahl salt-sensitive and salt-resistant rats and SHRs, for projection in human studies.…”

Effect of Synbiotic Therapy on Gut–Derived Uremic Toxins and the Intestinal Microbiome in Patients with CKD

“…Patients with CKD and ESRD frequently exhibit endotoxemia, the magnitude of which is directly related to severity of systemic inflammation (10). The primary source of circulating endotoxin in patients with CKD and CKD animals is the gastrointestinal tract.…”

Neurocritical Care for Patients with Kidney Dysfunction

“…Breakdown of the intestinal epithelial barrier due to loss of tight junction proteins has been described in CKD animals [73,74] and is likely responsible for the translocation of gut bacterial toxins into the systemic circulation [75,76], thus propagating systemic inflammation and cardiovascular disease [74]. Proposed pathways for intestinal tight junction breakdown include pro-inflammatory effects of elevated urea and deficiency of the transcription factor Nrf2 [74,77,78].…”

“…Proposed pathways for intestinal tight junction breakdown include pro-inflammatory effects of elevated urea and deficiency of the transcription factor Nrf2 [74,77,78]. Endotoxin (lipopolysaccharide), derived from the cell wall of Gram-negative bacteria, is measurable in the blood of dialysis patients and correlates with severity of systemic inflammation in the absence of clinically detectable infection [76]. Further, the gut microbiome is altered in CKD, leading to overgrowth of bacteria that produce uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide (TMAO) [74].…”