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Updated: Dec 24, 2025

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Beta-glucans in advanced CKD: role in endotoxaemia and inflammation
Jonathan Wong1,2, Yonglong Zhang3, Oscar Swift4
1Renal Research, East and North Herts NHS Trust, Coreys Mill Lane, Stevenage, SG1 4AB, UK. Jonathan.wong@nhs.net.
Background/Aims:
(1-3)-β-D glucans (BG) are cellular components of yeasts and fungi. Elevated blood levels may be an adjunct in diagnosing invasive fungal infection, though can be high in dialysis patients without fungaemia. BG can also induce false positive signals in endotoxin detection assays (Limulus Amoebocyte Lysate [LAL] assay). We explored the relationship between BG levels, renal impairment, endotoxaemia and inflammation.
Methods:
We measured serum BG levels, markers of inflammation and blood endotoxin levels in 20 controls, 20 with stages 1-3 chronic kidney disease (CKD), 20 with stages 4-5 CKD, 15 on peritoneal dialysis (PD) and 60 on haemodialysis (HD). Another 30 patients were studied before and after HD initiation.
Results:
BG levels increased with advancing CKD, being highest in HD patients, 22% of whom had elevated levels (> 80 pg/ml). Levels increased significantly following HD initiation. Levels also correlated positively with CRP, TNFα, IL-6 levels, independently of CKD stage. Blood endotoxin was detectable by LAL assays in 10-53% of the CKD cohort, being most prevalent in the HD group, and correlating positively with BG levels. Adding BG blocking agent to the assay reduced endotoxin detection confining it to only 5% of HD patients. Levels of inflammatory markers were higher in those with detectable endotoxin - whether false- or true positives.
Conclusion:
BG levels increased with decreasing renal function, being highest in dialysis patients. High BG levels were associated with false positive blood endotoxin signals, and with markers of inflammation, independently of CKD stage. The cause for high BG levels is unknown but could reflect increased gut permeability and altered mononuclear phagocytic system function.
Insights
(1-3)-β-D glucans (BG) increase with declining kidney function, particularly in dialysis patients. High BG levels correlate with inflammation and can cause false positive endotoxin tests, suggesting altered gut permeability in renal impairment.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Immunology
Background:
- (1-3)-β-D glucans (BG) are fungal cell wall components.
- Elevated BG levels can indicate invasive fungal infection but may also occur in dialysis patients.
- BG can interfere with endotoxin detection assays like the Limulus Amoebocyte Lysate (LAL) assay.
Purpose of the Study:
- To investigate the relationship between BG levels, renal impairment, endotoxaemia, and inflammation.
- To assess BG levels in patients with varying stages of chronic kidney disease (CKD) and on different dialysis modalities.
- To determine the impact of BG on endotoxin detection and its association with inflammatory markers.
Main Methods:
- Serum BG levels, inflammatory markers (CRP, TNFα, IL-6), and blood endotoxin were measured in controls and CKD patients (stages 1-5), including those on peritoneal dialysis (PD) and haemodialysis (HD).
- Patients were studied before and after HD initiation.
- LAL assays were performed with and without a BG blocking agent.
Main Results:
- BG levels significantly increased with advancing CKD, peaking in HD patients (22% elevated).
- BG levels correlated positively with inflammatory markers (CRP, TNFα, IL-6) and increased post-HD.
- Endotoxin was detected in 10-53% of CKD patients, most in HD, correlating with BG; a BG blocking agent reduced detection to 5% in HD patients, indicating false positives.
Conclusions:
- BG levels rise with decreasing renal function, are highest in dialysis patients, and correlate with inflammation.
- High BG levels are linked to false-positive endotoxin detection, suggesting potential gut permeability issues in renal impairment.
- The findings highlight the need to consider BG interference in endotoxin assays for patients with kidney disease and inflammation.
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