Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer: A Randomized Controlled Trial

Abstract

Background and objectives: Expanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer.

Design, setting, participants, & measurements: Clinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment.

Results: Among 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and β2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment.

Conclusions: Hemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level.

Clinical trial registry name and registration number: A Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

Keywords: ESKD; chronic dialysis; chronic inflammation; dialysis; end-stage kidney disease; hemodialysis; maintenance dialysis; randomized controlled trials; renal dialysis.

Graphical abstract

Figure 1.

Patient disposition. Enrollment, randomization, and completion of the clinical trial, including reasons for not completing the 24-week per protocol trial intervention, showing similar completion between the Theranova 400 and Elisio-17H randomization strata. FLC, free light chain; HD, hemodialysis; PD, peritoneal dialysis.

Figure 2.

Removal of middle molecules at 4 and 24 weeks. The reduction ratios of free λ light chains, complement factor D, free κ light chains, TNFα, and β2-microglobulin were significantly higher in the Theranova group compared with the Elisio-17H group (P<0.001 for all). For IL-6, the difference was not statistically significant.