Beta-glucans in advanced CKD: role in endotoxaemia and inflammation

Abstract

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.

Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress/mitochondrial ROS/glycolysis pathways

“…β-Glucan is a potent inducer of TI ( 2 , 19 ). β-Glucan was increased in CKD patients to play roles in promoting inflammation ( 108 ). Our data show that the receptor for β-glucan, dectin-1 ( CLEC7A ) ( 4 , 109 ), was significantly upregulated in CKD renal specimens ( Figure 8B ), which demonstrated the potential roles of the β-glucan/dectin-1 pathway in promoting inflammation in CKD.…”

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34

“…Then, this vicious cycle is possibly facilitated by gut fungi due to the enhanced serum BG with the presence of Candida in the gut. Interestingly, spontaneous glucanemia and endotoxemia (without systemic infection) in patients with CKD support the CKD-induced gut barrier defect [ 60 ] that might be correlated with gut dysbiosis. Indeed, gut fungi in 5/6Nx mice facilitated pathogenic Proteobacteria without alteration on Bacteroides and Firmicutes compared with non- Candida 5/6Nx.…”

<b><i>Candida</i></b> Administration Worsens Neutrophil Extracellular Traps in Renal Ischemia Reperfusion Injury Mice: An Impact of Gut Fungi on Acute Kidney Injury

“…The increased serum BG (beta-glucanemia) in uremic patients which is associated with the severity of uremia (uremia-induced inflammation) [ 46 ] and beta-glucanemia-induced inflammation might partly be responsible for systemic inflammation. Because BG is a major molecule of fungal cell wall, beta-glucanemia in patients with uremia might be due to gut translocation of BG from fungi in fecal contents.…”