Abstract

Hemodialysis patients with central venous catheters (CVCs) have chronic systemic inflammation, the source of which may be related to intraluminal bacterial biofilm. There is currently no non-invasive method to adequately evaluate intraluminal biofilm. Lipoteichoic acid (LTA) is a Gram-positive bacterial cell wall component that is spontaneously shed. The purpose of this study was to determine whether LTA could be quantified in biological samples and to evaluate potential relationships to markers of inflammation. Heparin-locked catheter aspirate was drawn from both the arterial and venous ports of each CVC prior to dialysis initiation. Venous blood from the dialysis circuit was collected 30 min after dialysis initiation. LTA was quantified in aspirate and plasma. Key markers of inflammation (interleukin-6, and hepcidin) and endothelial dysfunction (soluble vascular endothelial cadherin) were also determined in plasma samples. Catheter aspirate and systemic blood samples were obtained from 40 hemodialysis patients. The median (range) duration of catheter use was 130 (20–1635) days. Unexpectedly, median (range) plasma LTA concentrations (ng/mL) were significantly higher than catheter aspirate LTA concentrations [3.93 (0.25–15) vs. 2.38 (0.1–8.1), respectively, p = 0.01] in the majority (70%) of patients. Area under the receiver operator characteristic (ROC) curve showed good potential prognostic value of catheter aspirate LTA predicting systemic LTA concentrations with an area under the curve of 0.815 (95% CI, 0.68–0.95). A significant correlation was found between LTA and serum ferritin (r = 0.32, p = 0.04), however, there were no significant correlations between LTA and the other inflammation biomarkers assessed. LTA is quantifiable in aspirate and plasma of hemodialysis patients with CVCs and warrants further investigation to determine potential clinical application to intraluminal biofilm evaluation.

Highlights

  • Despite active initiatives to start hemodialysis with permanent vascular access, tunneled central venous catheter (CVC) use remains high at dialysis initiation and infection continues to be the second leading cause of death in end-stage renal disease (ESRD) patients [1, 2]

  • Several studies have shown that CVCs are rapidly colonized after insertion with Gram-positive organisms that can form intraluminal biofilm which can be a source of inflammation if planktonic bacteria or biofilm fragments enter the systemic circulation [5]

  • A principal component of the Gram-positive bacteria cell wall is lipoteichoic acid (LTA) [7] which is a key mediator of inflammation in Gram-positive infections, activating NFκB via the toll-like 2 (TLR2) receptor resulting in production of pro-inflammatory cytokines. [8, 9] LTA is a transmembrane glycoprotein that is released from the bacteria cell wall and could be a potential biomarker to non-invasively assess catheter biofilm burden

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Summary

Introduction

Despite active initiatives to start hemodialysis with permanent vascular access, tunneled central venous catheter (CVC) use remains high at dialysis initiation and infection continues to be the second leading cause of death in end-stage renal disease (ESRD) patients [1, 2]. Lipoteichoic Acid in Dialysis Patients concentrations, both of which are biomarkers of inflammation with strong associations with mortality in the hemodialysis population [3, 4]. A validated biomarker of intraluminal biofilm could be utilized to inform clinical decisions such as accelerating permanent vascular access placement, catheter removal/replacement or installation of antimicrobial lock solutions [11,12,13]. This pilot, proof of concept study sought to determine whether concentrations of LTA in catheter aspirate and the systemic circulation of hemodialysis patients with CVCs could be quantified. Relevant biomarkers of inflammation and endothelial permeability were evaluated to explore potential associations with LTA concentrations

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