BACKGROUND:Conventional hemodialysis (HD) remains limited in removing middle and large uremic toxins and is associated with substantial residual morbidity and mortality. On-line postdilution hemodiafiltration (HDF) has emerged as an advanced modality combining diffusion and convection to enhance solute clearance and clinical outcomes. OBJECTIVES:To describe the mechanistic basis, technical architecture, and operational determinants of HDF and to position high-volume postdilution HDF as a reference therapy in modern dialysis care. METHODS:Narrative review of physiological principles, transport mechanisms, and technical requirements underpinning HDF, integrated with current clinical evidence and engineering considerations. RESULTS:Postdilution HDF combines diffusive and convective transport within a single dialyzer, enabling superior clearance of middle- and large-molecular-weight solutes compared with high-flux HD, combined even with a modestly improved small-solute removal. Convective efficiency is governed by the interplay between blood flow, plasma water flow, and filtration fraction, with optimal patient outcomes achieved at high convective volumes (i.e., ≥23 L/session), as there exists a dose-dependent correlation. The technique relies on a robust and inherently safe technical ecosystem, including ultrapure water systems, on-line production of sterile substitution fluid through multistage ultrafiltration, and advanced dialysis machines enabling precise volumetric control and real-time flow and pressure monitoring. High-volume postdilution HDF is associated with improved hemodynamic stability, reduced inflammation, and better clinical outcomes, including lower mortality and hospitalization rates, with a clear dose-response relationship. CONCLUSIONS:Postdilution HDF represents a paradigm shift in extracorporeal therapy, integrating optimized transport mechanisms with advanced technical infrastructure to deliver a broader and more effective dialytic dose. When properly implemented, high-volume postdilution HDF should be considered a reference standard for personalized, efficient, and sustainable dialysis care.
Hemodialysis (HD) is one of the major treatment modalities for patients with kidney failure; moreover, there are many alternatives, such as expanded HD (HDx) and on-line hemodiafiltration (HDF). This chapter begins with a historical overview of these treatment modalities and discusses the current mainstream treatments in Europe, North America, and Japan. The "protein-losing" dialysis membrane was first realized in Japan in the early 1980s, and treatment using these membranes has evolved into HDx and/or on-line HDF with an albumin leakage range of 3-6 g, which corresponds to a 30-40% reduction rate in α1-microglobulin levels over the course of a single dialysis session that reduces or eliminates many clinical symptoms. Whether albumin-leaking membranes are "friends or foes" depends on the patient's general conditions; however, based on our more than 40 years of clinical experience in Japan, they are generally considered "friends."
Clinical outcomes in hemodialysis remain suboptimal, and it is imperative to make any effort to improve the quality of life of dialysis patients. Unsatisfactory results have been correlated with the accumulation of uremic retention products in the middle- to high-molecular-weight range inadequately removed by current dialytic techniques. These toxins cause and worsen inflammation, immune dysfunction, and various pathological effects. This results in high morbidity and mortality with unacceptable rates of cardiovascular events, accelerated atherosclerosis, infection, and multiple organ dysfunction. Expanded hemodialysis (HDx) with a modern medium cut-off (MCO) membrane, which closely mimics the native kidney, significantly improves removal of such uremic toxins. Current evidence has shown that the safety, simplicity, superior performance, and efficacy of HDx with the MCO membrane translate to improved clinical outcomes.
Hemodialysis and related extracorporeal therapies utilize filters (dialyzers) comprising hollow fiber membranes to achieve solute and water removal. While membrane classification schemes based on composition and water permeability are the historical standard, recent membrane advances have created new perspectives. In particular, the introduction of medium cut-off membranes with mean pore sizes substantially larger than those typical of standard highly permeable membranes for a new therapy (expanded hemodialysis [HDx]) necessitates the development of refined schemes that clearly define the new options available to clinicians. These new approaches will be highlighted along with the interaction between membrane pore size, water permeability, and convective large molecule clearance through the mechanism of internal filtration. The broader molecular weight removal spectrum made possible by these larger pore membranes in HDx will be presented in the context of on-line hemodiafiltration (OL-HDF), both of which rely almost exclusively on convection for large molecule clearance. Finally, the ongoing debate about the appropriate balance between large solute clearance and albumin loss for both HDx and OL-HDF is discussed.
The most common type of dialyzer worldwide is currently the synthetic membrane used in high-flux dialyzers. In Japan, however, super high-flux dialyzers have long been the mainstream, and those with enlarged pore sizes can remove large-molecule toxins such as α1-microglobulin. Up to 2012 in Japan, dialyzers were classified into five types based on β2-microglobulin (β2MG) clearance: Type I (<10 mL/min), Type II (≥10-30), Type III (≥30-50), Type IV (≥50-70), and Type V (≥70). Type IV and Type V dialyzers are defined as super high-flux dialyzers and have been associated with good prognosis. In the new classification, dialyzers with a β2MG clearance <70 mL/min are classified as Type I, and those with a clearance of ≥70 mL/min are classified as Type II. Furthermore, for the albumin sieving coefficient, values below and above a boundary value of 0.03 were subdivided into Type a (albumin impermeable/low permeable) and Type b (albumin permeable), respectively. Based on β2MG clearance and albumin sieving coefficient, dialyzers are then classified into four types: I-a, I-b, II-a, and II-b. Type I-a is denoted as standard flux, Type I-b as high flux-albumin leaking, Type II-a as super high flux, and Type II-b as albumin leaking-super high flux. In addition, Type S dialyzers have been defined, which have high biocompatibility, improved solute removal efficiency by adsorption, and anti-inflammatory and antioxidant effects. In the current classification, super high-flux dialyzers with a β2MG clearance of ≥70 mL/min and Type S dialyzers are suggested to contribute to improved prognosis. This review provides an overview of the new classification of dialyzers in Japan.
