#2715 AN EXPLORATORY STUDY OF GUT PERMEABILITY IN SUBJECTS ON HAEMODIALYSIS: RESPONSE TO AN ORAL BETA-D-GLUCAN LOAD
Authors: Swift Oscar , Finkelman Malcolm , Zhang Yonglong , Doctolero Eunice , Javier Chadd , Gilbert Mikky , Sridharan Sivakumar , Farrington Kenneth , Vilar Enric 
Published: June 2023

Abstract

Background and Aims
End stage kidney disease (ESKD) is associated with chronic inflammation. A combination of increased gut permeability and impaired hepatic clearance of gut-derived toxins are likely contributory factors to chronic inflammation in ESKD. Gut permeability assessment in kidney impairment is complex as traditional gut permeability probe concentrations are significantly influenced by residual kidney function. (1-3)-β-D glucans (BDG) are glucose polymers found in dietary plant material and also fungi and bacteria. BDG predominantly undergo reticuloendothelial (primarily hepatic) clearance. BDG ingested in the form of fibre are not well absorbed from the small intestine. Elevated serum BDG levels have been previously observed in chronic kidney disease and may reflect systemic translocation of dietary and gut derived microbial fragments from the portal system. This study aimed to establish if there were differences in serum BDG concentrations in individuals with normal kidney function and ESKD following ingestion of a BDG rich meal.

Method
20 participants with ESKD receiving haemodialysis via an arteriovenous fistula with evidence of inflammation (a median baseline serum C-reactive protein (CRP) ≥5mg/L over the previous 3 months) and 20 participants with normal kidney function (NKF) were studied. Participants with active infection, autoimmune disease, gastrointestinal disease and hyperkalaemia were excluded. All participants followed a low fibre diet for 48 hours and fasted for 12 hours prior consuming a BDG-rich drink that delivered approximately 10μg/gram of BDG. In the ESKD cohort, the drink was consumed immediately prior to a dialysis session following a 1-day interdialytic gap. In addition to standard of care blood tests, serum BDG levels were measured at baseline, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours and 48 hours. Serum BDG measurements were analysed with the Fungitell® assay (Associates of Cape Cod, Inc). Faecal calprotectin and faecal alpha-1-antitrypsin were also analysed.

Results
20 participants with ESKD receiving haemodialysis (mean age 66.8 years) and 20 participants with NKF (mean age 44.6 years) were recruited. Serum BDG levels were significantly higher at baseline in the ESKD group (29.6pg/ml in the NKF group versus 67.1pg/ml in the ESKD group, p = 0.001) and at all other timepoints throughout the study period (see Fig. 1). There were no significant difference in change from baseline BDG levels between groups. Individual BDG levels taken post meal ingestion are shown in Fig. 2. Baseline serum BDG levels correlated strongly with median baseline high sensitivity CRP over 3 months (p = 0.001) however this relationship was not present when the two groups were examined separately. Faecal calprotectin and faecal alpha-1-antitrypsin did not correlate with baseline serum BDG measurements (p = 0.93, p = 0.78, respectively).

Conclusion
Elevated BDG levels are observed in ESKD and increase both during and immediately following dialysis after ingestion of a BDG load. In addition to dietary BDG, translocation of gut-derived microbial BDG into the systemic circulation may play an important role in contributing to systemic inflammation observed in advanced kidney disease. Elevated BDG may reflect increased gut permeability which may be secondary to uraemic toxin related gut barrier dysfunction or splanchnic ischaemia related to ultrafiltration.