Expanded Hemodialysis with Theranova 500 Improves Dialysis Adequacy and Blunts Inflammation: A 24-Week Quasi-Randomized Trial

Background/Objectives: Uremic middle molecules contribute to chronic inflammation and symptom burden in hemodialysis patients. The Theranova 500 medium-cutoff (MCO) dialyzer enhances clearance of larger uremic toxins and may offer clinical advantages. We hypothesized that Theranova 500 would improve dialysis adequacy (spKt/V), attenuate inflammation (CRP), and provide targeted improvement in symptom burden compared with the high-flux Revaclear 500. Methods: We conducted an open-label, prospective, quasi-randomized controlled trial including forty prevalent adult hemodialysis patients from two centers in Israel (Barzilai and Sheba Medical Centers). Patients were sequentially allocated 1:1 to Theranova 500 or Revaclear 500. Demographic, laboratory, and patient-reported outcomes (KDQOL-SF, Dialysis Symptom Index) were assessed at baseline and week 24. Within-group changes were analyzed using paired tests, and between-group differences using ANCOVA adjusted for baseline values. Safety monitoring included adverse events, dialyzer reactions, hospitalizations, and mortality. Results: Theranova 500 significantly increased mean spKt/V (1.24 ± 0.33 to 1.40 ± 0.36; p = 0.025), while Revaclear showed no significant change. CRP remained stable in the Theranova group but rose nearly threefold in the Revaclear group by week 24 (p < 0.001). Albumin, dry weight, anemia and mineral bone parameters remained stable in both groups. Total cholesterol increased modestly in the Theranova arm without nutritional compromise. Symptom-level analysis showed improvement in irritability, restless leg, dry skin, chest pain, and diarrhea with Theranova, whereas global KDQOL-SF domain scores improved similarly in both groups. No non-serious adverse events, hypersensitivity reactions, or dialyzer-related intolerance was observed. Hospitalizations (n = 8 per group) and mortality (two per group) were identical. Conclusions: Over 24 weeks, Theranova 500 MCO dialyzer improved dialysis adequacy and prevented the rise in inflammatory markers seen with Revaclear without compromising nutrition or safety. Targeted improvement in specific uremic symptoms suggests potential clinical benefit beyond small-molecule clearance. These findings support the safety and clinical utility of expanded hemodialysis and highlight the need for larger, fully randomized trials to validate these results.