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

Usama Feroze,Kamyar Kalantar-Zadeh,Kevin A Sterling,Miklos Z Molnar,Nazanin Noori,Debbie Benner,Vallabh Shah,Rama Dwivedi,Kenneth Becker,Csaba P Kovesdy,Dominic S Raj

doi:10.1053/j.jrn.2011.05.004

Abstract

Lipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram-negative bacteria. Subclinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis (HD) 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. In this cohort study, endotoxin levels were measured in 306 long-term HD patients who were then followed up for a maximum of 42 months. Soluble CD14 and cytokines levels were also measured. The mean (±SD) endotoxin level was 2.31 ± 3.10 EU/mL (minimum: 0.26 EU/mL, maximum: 22.94 EU/mL, interquartile range: 1.33 EU/mL, median: 1.27 EU/mL). Endotoxin correlated with C-reactive protein (r= 0.11, P< .04). On multivariate logistic regression analysis, high body mass index and low high-density lipoprotein (HDL) cholesterol levels were associated with higher endotoxemia (endotoxin below or above of median). In multivariate Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the third quartile versus first quartile were associated with a trend toward increased hazard ratio for death (hazard ratio: 1.83, 95% confidence interval: 0.93 to 3.6, P = .08). In this HD cohort, we found associations between endotoxemia and C-reactive protein, body composition, and HDL. Moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to assess the effect of endotoxemia on mortality in dialysis population.

Highlights

End Stage Renal Disease (ESRD) patients have increased morbidity and mortality compared to the general population
On multivariate logistic regression analysis, high body mass index (BMI) and low HDL cholesterol levels were associated with higher endotoxinemia
In multivariable Cox regression analysis adjusted for casemix 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)

Summary

Introduction

End Stage Renal Disease (ESRD) patients have increased morbidity and mortality compared to the general population. Infection is the second most important cause of the increased mortality seen in these ESRD patients [1]. The incidence rate of bacterial infections in ESRD patients is one episode per 100 patient months [3, 4]. These bacterial infections are often life threatening given the increased susceptibility of uremic patients to infection due to their immune dysfunction[5]. While Staphylococcus aureus is the major pathogenic organism [4] responsible for infections in dialysis patients, it has been found that endotoxemia due to gram-negative organisms is a potential source of inflammation in these ESRD patients. While Staphylococcus aureus is the major pathogenic organism [4] responsible for infections in dialysis patients, it has been found that endotoxemia due to gram-negative organisms is a potential source of inflammation in these ESRD patients. [6]

Methods

Results

Conclusion