PHILIPPA JAMES10, OJAS DIXIT2,3, MARY ANN NICDAO4, BRETT MCWHINNEY5, JORDAN STANFORD2,6, KAMAL SUD4,7, SCOTT READ1,8, GOLO AHLENSTIEL1,8, KELLY LAMBERT2,6, CLAIRE O’BRIEN9, KATRINA CHAU1,4
1Western Sydney University, Sydney, Australia, 2Illawarra Health and Medical Research Institute, Australia, 3School of Chemistry and Molecular Bioscience, Molecular Horizons, University of Wollongong, Wollongong, Australia, 4Western Renal Services (Western Sydney and Nepean Blue Mountains Local Health Districts), Sydney, Australia, 5Analytical Chemistry Unit, Chemical Pathology, Pathology Queensland, Australia, 6Faculty of Science, Medicine and Health, School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, Australia, 7Nepean Clinical School, Faculty of Medicine and Health, The University of Sydney, Australia, 8Liver Immunology Group, Storr Liver Centre, Westmead Institute for Medical Research, Australia, 9University of Canberra, Australia, 10School of Medicine, Western Sydney University, New South Wales, Australia, 10School of Medicine, Western Sydney University, New South Wales, Australia
Aim: To identify relationships between uraemic toxins, symptoms and the gut microbiota in advanced chronic kidney disease (CKD).
Background: Uraemic toxins produced by gut microbial metabolism of amino acids contribute to the uraemic syndrome. There is limited data on the relationship between uraemic toxins, symptoms and the gut microbiota.
Methods: Baseline data of adults at commencement of peritoneal dialysis participating in a longitudinal observational study of the peritoneal dialysate microbiome were analysed. Clinical data and symptom scores using iPOS-Renal was recorded. Plasma p-Cresyl sulfate (pCS), indoxyl sulfate (IS) and trimethylamine N-oxide (TMAO) were measured. Gut microbiota was determined using 16S rRNA sequencing. Associations between variables and relative abundances at the genus level were tested using multivariate associations with linear models in R version 4.1.3.
Results: Thirty-three patients were included (median age 67 (range 22-80), median eGFR 7 ml/min/1.73m2 (range 3-13), 76% were male and primary cause of CKD was diabetes mellitus in 48.5%). Weakness and lack of energy were the most severe and frequently reported (75.8%) symptoms. TMAO correlated with diarrhoea (Spearman’s rank=0.310, p=0.01). Clostridium innocuum group (q=0.03) and Acetanaerobacterium genus (q=0.002) were associated with high iPOS-Renal score. Alpha diversity was positively associated with total pCS (pShannon=0.004 and pFaith’s=0.002) and free pCS (pShannon=0.01 pFaith’s=0.002). Two clusters of patients based on profile of uraemic toxins showed significant difference in beta-diversity (Bray-Curtis p=0.046). Several specific genera of the Firmicutes phyla were also associated with higher pCS levels.
Conclusions: Alpha diversity and specific taxa associate with concentrations of uraemic toxins. Uraemic toxins and specific taxa are associated with specific symptoms in patients with advanced CKD. Further study is required to validate these findings and inform future therapeutic strategies
Biography:
Philippa James is currently a final year medical student at Western Sydney University. Prior to this, she obtained her Bachelor of Medical Research from Western Sydney University. Philippa is interested in both research and clinical medicine. She plans to pursue a career in nephrology.