Manuela Stauss-Grabo

Hemodiafiltration (HDF) combines diffusion and convection to enhance solute removal compared with hemodialysis (HD). While widely adopted in Europe and parts of Asia, uptake elsewhere remains limited due to regulatory, reimbursement, and infrastructural constraints. Recent randomized trials, large observational studies, and meta-analyses have renewed interest in HDF, particularly post-dilution HDF achieving convection volumes of ≥23 L/session, in which the most consistent clinical benefits have been observed. This review summarizes the mechanistic rationale, clinical effects, and safety profile of high-volume HDF. Compared with HD, HDF provides consistently superior removal of middle molecules, whereas clearance of protein-bound uremic toxins (PBUTs) remains constrained by albumin binding and compartmental redistribution, resulting in only modest or variable advantages. Emerging strategies aimed at releasing or capturing PBUTs may address this gap. Beyond solute removal, evidence suggests that HDF may lower micro-inflammation by enhanced clearance of inflammatory mediators and reduced immune activation. When delivered with adequate infrastructure, monitoring, modern equipment, ultrapure fluids, trained staff, appropriate vascular access, and anticoagulation, high-volume HDF has a favorable safety profile and is associated with fewer intradialytic hypotension (IDH) events and improved treatment tolerability. Available evidence has not identified a consistent excess risk of device- or infection-related complications, although comparative data remain limited. Overall, current evidence supports clinically relevant advantages of high-volume HDF under optimal treatment conditions. However, important challenges remain, particularly the limited removal of PBUTs, underscoring the need for further innovation in uremic toxin management.

Innovation in dialysis care is fundamental to improve well-being and outcomes of patients with end-stage kidney disease. The dialyzer is the core element of dialysis treatments, as it largely defines which substances are removed from the patient’s body. Moreover, its large surface size is the major place of interaction of the patient’s blood with artificial surfaces and thus may lead to undesired effects such as inflammation or coagulation. In the present article we summarize the development path for a new dialyzer, including in vitro and clinical evidence generation. We use the example of the novel FX CorAL dialyzer, which has recently entered European and US markets, to show which steps are needed to develop and characterize a new dialyzer. The FX CorAL dialyzer includes a new hydrophilic membrane, which features reduced protein adsorption, sustained performance, and an improved hemocompatibility profile, characterized in numerous in vitro and clinical studies. Safety evaluations revealed a favorable profile, with low incidences of adverse device effects. Insights gained from both in vitro and clinical studies contribute to the advancement of dialyzer development, ultimately leading to improved patient care.

While efficient removal of uremic toxins and accumulated water is pivotal for the well-being of dialysis patients, protein adsorption to the dialyzer membrane reduces the performance of a dialyzer. Hydrophilic membrane modification with polyvinylpyrrolidone (PVP) has been shown to reduce protein adsorption and to stabilize membrane permeability. In this study we compared middle molecule clearance and filtration performance of nine polysulfone-, polyethersulfone-, and cellulose-based dialyzers over time. Protein adsorption was simulated in recirculation experiments, while β2-microglobulin clearance as well as transmembrane pressure (TMP) and filtrate flow were determined over time. The results of this study showed that β2-microglobulin clearance (−7.2 mL/min/m²) and filtrate flow (−54.4 mL/min) decreased strongly during the first 30 min and slowly afterwards (−0.7 mL/min/m² and −6.8 mL/min, respectively, for the next 30 min); the TMP increase (+37.2 mmHg and +8.6 mmHg, respectively) showed comparable kinetics. Across all tested dialyzers, the dialyzer with a hydrophilic modified membrane (FX CorAL) had the highest β2-microglobulin clearance after protein fouling and the most stable filtration characteristics. In conclusion, hydrophilic membrane modification with PVP stabilizes the removal capacity of middle molecules and filtration performance over time. Such dialyzers may have benefits during hemodiafiltration treatments which aim to achieve high exchange volumes.