Targeting Protein-Bound Uremic Toxins: A Dual Approach with Medium Cut-Off Membrane Dialysis and a Dietary...

Background/Objectives: Protein-bound uremic toxins (PBUTs), particularly p-cresyl sulfate (PCS) and indoxyl sulfate (IS), are associated with cardiovascular toxicity and increased mortality. Conventional hemodialysis (HD) removes PBUTs poorly, and the efficacy of medium cut-off (MCO) dialyzer membranes remains uncertain. Furthermore, PBUT production is influenced by gut microbial metabolism and can be modified through diet. We hypothesized that MCO dialysis would provide superior clearance of PCS and IS compared with online hemodiafiltration (OL-HDF), and that combining MCO dialysis with increased dietary fiber and short-chain fatty acid (SCFA) intake would further reduce PBUT levels. Methods: In this prospective randomized trial, 62 maintenance HD patients underwent a 2-week wash-in period with high-flux HD (HF-HD) and were then randomized to MCO-HD (EXP) or OL-HDF (CON). After a 4-week intervention with the assigned dialysis modality, both groups continued with the same dialysis treatment and received an 8-week dietary intervention consisting of 19 g/day fiber and 1 g/day sodium propionate. The study concluded with a 4-week wash-out period on HF-HD. Primary outcomes were total serum PCS and IS levels measured at four timepoints. Results: Fifty-two patients completed the study. No significant changes in PCS or IS were observed after the dialysis-only intervention. PCS levels remained stable throughout the study. When the aligned dialysis regimen was combined with the dietary intervention, IS levels were significantly lower in the CON than in the EXP group (31.5 ± 10.3 vs. 42.0 ± 15.8 µmol/L; p = 0.006), with a partial rebound after wash-out in the CON group (39.6 ± 20.9 µmol/L; p = 0.003). Conclusions: While MCO-HD and OL-HDF had a similar effect on serum PCS and IS concentrations, only OL-HDF combined with the dietary intervention significantly reduced IS levels.