Uremic Toxins and Blood Purification: A Review of Current Evidence and Future Perspectives

Abstract

Accumulation of uremic toxins represents one of the major contributors to the rapid progression of chronic kidney disease (CKD), especially in patients with end-stage renal disease that are undergoing dialysis treatment. In particular, protein-bound uremic toxins (PBUTs) seem to have an important key pathophysiologic role in CKD, inducing various cardiovascular complications. The removal of uremic toxins from the blood with dialytic techniques represents a proved approach to limit the CKD-related complications. However, conventional dialysis mainly focuses on the removal of water-soluble compounds of low and middle molecular weight, whereas PBTUs are strongly protein-bound, thus not efficiently eliminated. Therefore, over the years, dialysis techniques have been adapted by improving membranes structures or using combined strategies to maximize PBTUs removal and eventually prevent CKD-related complications. Recent findings showed that adsorption-based extracorporeal techniques, in addition to conventional dialysis treatment, may effectively adsorb a significant amount of PBTUs during the course of the sessions. This review is focused on the analysis of the current state of the art for blood purification strategies in order to highlight their potentialities and limits and identify the most feasible solution to improve toxins removal effectiveness, exploring possible future strategies and applications, such as the study of a synergic approach by reducing PBTUs production and increasing their blood clearance.

Beta-2 microglobulin removal with postdilution online hemodiafiltration - comparison of three different dialysis membranes

“…The target 2m predialysis level of <30mg/L was met in 70% of our study population, while 36.67% even had predialysis β 2 m level < 25ml/L [11,[23][24][25][26]. The highest β2m removal rate in our study population was achieved with FX CorDiax 800 dialyzer, even though the difference was not statistically significant.…”

“…Previous studies have demonstrated that the average β2m removal rate ranges from 50-60% with regular high-flux HD, to 70% with medium cut-off membranes, to 80-85% with high volume (Vconv > 22 L / dialysis session) post-dilution OL-HDF [23][24][25][26]. The somewhat lower β2m reduction ratio achieved with post-dilution OL-HDF in our study population, ranging from 70.04-74.69%, can be explained by lower than average Vconv and Qb in our study population (Table 1).…”

Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

“…Several of the associated uremic toxins originate in the intestines by bacterial metabolization of dietary products. Some of these intestinally generated uremic toxins are bound to proteins in the circulation, and their removal by dialysis is expensive and remains insufficient [24,25]. Alternative measures to decrease levels of these uremic toxins, preferably targeting uremic toxins at their origin, are needed.…”

Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review

“…The poor removal of PBUTs with conventional HD is evidenced by the fact that pre-dialysis levels of IS and pCS have been found to be as much as 116-fold and 41-fold higher, respectively, than in age-matched healthy controls, while pre-dialysis concentrations of non-protein-bound solutes with comparable molecular weight, such as urea and creatinine, were only 5- and 13-fold higher, respectively [ 8 ]. Strong protein-binding results in a low reduction ratio of 20 to 35% for prototypical PBUTs [ 9 ], while the reduction ratio for small non-protein-bound solutes such as urea is around 80% during a conventional 4 h hemodialysis session [ 10 ]. The reduction ratio of a solute is a measure of dialysis session efficacy and indicates the percentage reduction in total serum concentration for this solute during a given dialysis duration.…”