Intestinal Barrier Disturbances in Haemodialysis Patients: Mechanisms, Consequences, and Therapeutic Options

Abstract

There is accumulating evidence that the intestinal barrier and the microbiota may play a role in the systemic inflammation present in HD patients. HD patients are subject to a number of unique factors, some related to the HD process and others simply to the uraemic milieu but with common characteristic that they can both alter the intestinal barrier and the microbiota. This review is intended to provide an overview of the current methods for measuring such changes in HD patients, the mechanisms behind these changes, and potential strategies that may mitigate these modifications. Lastly, intradialytic exercise is an increasingly employed intervention in HD patients; however the potential implications that this may have for the intestinal barrier are not known; therefore future research directions are also covered.

The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat

“…A limitation of the present study is that we did not attain training history or current training status from participants, it has been speculated that regular training may be protective against exercise-induced changes in intestinal permeability through an up-regulation in HSP [ 22 , 46 ]. However, this has yet to be reliably demonstrated [ 47 ], and furthermore in the current study there was little variation for values (SD < 5 mL kg −1 min −1 ) indicating a similar level of aerobic fitness for participants in the study (whom were all regular exercisers).…”

“…However, there are issues pertaining to the collection and analysis of blood samples [through the limulus amoebocyte lysate assay (LAL)], in addition to the detection of LPS, suggesting that this marker may not be ideal [ 18 , 19 ]. Some clinical studies have measured intestinal-derived circulating bacterial DNA via 16S rDNA PCR assays to indicate changes in intestinal permeability [ 19 – 22 ], which has been suggested to be more specific to targeted bacterial strains and can overcome some of the sensitivity and specificity issues that exist for the LPS LAL assays. However, circulating bacterial DNA (as a marker of bacterial translocation) has not previously been assessed within an exercise and heat stress model.…”

Overhydration, underhydration, and total body sodium: A tricky “ménage a trois” in dialysis patients

“…Cerebral infarcts, atrophy, and leukoaraosis are common finding in dialysis patients, with successive long‐term consequences of cognitive decline, dementia, and stroke . Hypoperfusion is also associated with translocation of endotoxins across the gut wall . These endotoxins are a robust proinflammatory stimulus related leading to malnutrition and wasting; it impacts all of the inflammation‐related adverse effects (from malnutrition to cardiovascular outcomes) seen in dialysis patients …”

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

“…Although we were unable to detect a difference between our high-risk and low-risk HD patients this may have been due to the small sample size or that our high risk HD patients were not experiencing significantly worse intra-dialytic hypotension compared to low-risk patients. Advanced CKD may impair intestinal barrier function and result in translocation of bacterial products into the circulationperhaps exacerbated by intradialytic gut hypo-perfusion [13,29,30]. Similarly, intestinal mucosal barrier damage and translocation has been described in end-stage kidney disease.…”

“…Patient considered to be high-risk had chronic unexplained inflammation indicated by a raised CRP > 5 mg/L, measured on two separate occasions at least 1 month apart during the 3 months prior to study recruitment together with either a high ultrafiltration requirement (rate > 10 mL/kg/hr) (11) or pre-or post-dialysis systolic BP < 100 mmHg within the week prior to study recruitment. Patients with high ultrafiltration requirements or low blood pressure are at risk of intra-dialytic hypotension and may predispose to endotoxemia driven by gut hypoperfusion [13][14][15]. Low-risk patients had none of these features.…”