Abstract
Background and Aims
Cognitive impairment is very common in dialysis patients, with negative effects on quality of life and mortality. In neurodegenerative conditions (Alzheimer, Parkinson) a gut-brain axis has been identified; however, there is no information about the relationship of gut microbiota alterations and presence of cognitive impairment in chronic kidney disease. The aim was to associate the gut microbiota profile with the cognitive function in patients on automated peritoneal dialysis (APD).
Method
Cross-sectional study in 39 APD patients; those with visual or mental disabilities, psychiatric or neurodegenerative diseases, inflammatory causes of ESRD, with active infections (including peritonitis), on anti-inflammatory drugs or antibiotics, were excluded. All patients had a clinical, biochemical, nutritional and dialysis adequacy evaluation, and were classified according to the presence of cognitive impairment using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected and immediately stored at -80 ºC. DNA extraction was performed with Quick-DNA Fecal/Soil Microbe Miniprep Kit (Zymo Research). Subsequently, V3 and V4 regions of 16S rRNA were sequenced using illumina platform. Statistical analysis: Student t test and χ2 were used to compare quantitative and qualitative variables, respectively. Quantitative Insights Into Microbial Ecology (QIIME) pipeline and Linear Discriminant Analysis Effect Size (LEfSe) were employed for bioinformatic analysis.
Results
Eighty-two percent of subjects were male, mean age 47 ± 24 years, and dialysis vintage 11 (7-48) months. Sixty-four percent of patients had cognitive impairment. Patients with cognitive impairment were significantly older (53 ± 16 vs 38 ± 14, p=0.006), had higher frequency of diabetes mellitus (56% vs 21%, p=0.04), and had lower creatinine concentrations (11.3 ± 3.7 vs 14.9 ± 5.4, p=0.02) compared to patients with normal cognitive function. No differences were found in other biochemical, nutritional or dialysis adequacy variables.
A total of 38,083 sequences per patient were obtained after the microbiome analysis. LEfSe analysis showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter, and Anaerotruncus in patients with cognitive impairment. In contrast, patients without cognitive impairment were characterized by Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) > 2.5; p < 0.05).
Conclusion
Cognitive impairment was present in two-thirds of these APD patients. Odoribacter and Anaerotruncus were significantly more abundant in patients with cognitive impairment than in those with normal function. Such gut bacteria might enhance cognitive impairment as have been described to increase the uremic toxin production and activation of inflammatory pathways in the central nervous system. This is the first study providing evidence than brain and behavior might be influenced by the gut-brain axis in dialysis patients.
Indoxyl Sulfate Elimination in Renal Replacement Therapy: Influence of Citrate- versus Acetate-Buffering Component during Bicarbonate Dialysis
