BACKGROUND: Chronic micro-inflammation in patients with end-stage renal disease (ESRD) is a significant driver of cardiovascular complications and diminished quality of life. While standard hemodialysis (SHD) effectively manages small-molecule clearance, its ability to remove medium-to-large uremic toxins-the primary catalysts of systemic inflammation-remains limited. This study aimed to evaluate the comparative clinical benefits of hemodiafiltration (HDF) and hemoperfusion (HDP) relative to SHD, specifically focusing on inflammatory control, dialysis adequacy, and patient safety. METHODS: This was a 10-week, single-center, non-randomized prospective observational study evaluating 365 end-stage renal disease (ESRD) patients divided into three cohorts: standard hemodialysis (SHD, n = 145, thrice-weekly), online hemodiafiltration (HDF, n = 115, twice-weekly hemodialysis plus once-weekly HDF), and hemoperfusion (HDP, n = 105, twice-weekly hemodialysis plus once-monthly hemoperfusion). Primary endpoints were restricted to short-term surrogate outcomes, including shifts in serum inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)) and clearance adequacy indices (Kt/V, URR). RESULTS: Baseline characteristics were well-balanced across all three cohorts. Following 10 weeks of treatment, the HDF (84.2%) and HDP (77.1%) groups demonstrated significantly higher effective treatment rates (defined by clinical symptom improvement and biochemical stability, a composite of symptomatic improvement and biochemical stability) compared to the SHD group (61.4%; p < 0.05). Advanced modalities achieved increased association with biomarker reduction of middle-molecule toxins, with HDF showing the most profound reductions in IL-6, TNF-α, and CRP (p < 0.001). Dialysis adequacy was significantly improved in the HDF group, which showed the highest increases in dialysis adequacy. While the incidence of acute complications such as hypotension and muscle cramps did not differ significantly between groups, both HDF and HDP cohorts reported a notable reduction in post-dialysis fatigue compared to SHD (14% and 16% vs. 19%, respectively). However, HDF and HDP cohorts experienced lower incidences of cognitive dysfunction. CONCLUSIONS: Over a 10-week observation framework, advanced hybrid modalities (HDF and HDP) are independently associated with superior clearance of middle-to-large molecular uremic toxins and attenuated systemic inflammation compared to SHD. However, these short-term surrogate improvements did not translate into a statistically significant reduction in clinical adverse events or post-dialysis fatigue, indicating the need for long-term longitudinal evaluation.
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