Francisco Maduell, Isabel Galcerán, Elena Cuadrado-Payán, José Jesús Broseta
{"title":"On-Line High-Volume Hemodiafiltration: Current Evidence and Clinical Outcomes.","authors":"Francisco Maduell, Isabel Galcerán, Elena Cuadrado-Payán, José Jesús Broseta","doi":"10.1159/000552910","DOIUrl":"https://doi.org/10.1159/000552910","url":null,"abstract":"<p><p>Despite continuous technological advances in dialysis therapy, patients with kidney failure undergoing maintenance hemodialysis continue to experience high morbidity and mortality, largely driven by cardiovascular disease and chronic inflammation. Conventional hemodialysis efficiently removes small solutes but has limited capacity to eliminate middle molecules and protein-bound uremic toxins that contribute to cardiovascular complications. On-line hemodiafiltration (OL-HDF) combines diffusive and convective transport, improving the clearance of a wider range of uremic toxins. Beyond its effects on solute removal, OL-HDF has been associated with improvements in several intermediate clinical outcomes, including better control of mineral metabolism, reduced inflammation, improved endothelial function, reduces the risk of intradialytic hypotension, and probable benefits in anemia management, nutritional status, and patient-reported quality of life. Over the past 3 decades, clinical research has evolved from mechanistic studies to randomized controlled trials and large-scale observational analyses evaluating hard clinical outcomes. Secondary analyses of clinical studies consistently identify convective volume as the effective \"dose\" of OL-HDF, demonstrating survival benefits when it exceeds 23 L per session. This chapter reviews the current clinical evidence on OL-HDF, including randomized trials, pooled analyses, real-world data, and translational outcomes, and discusses how treatment delivery and convective dose influence the clinical effectiveness of this modality.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"77-93"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Albumin-Leaking Membranes: Friends or Foes?","authors":"Akihiro C Yamashita","doi":"10.1159/000552905","DOIUrl":"https://doi.org/10.1159/000552905","url":null,"abstract":"<p><p>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 α<sub>1</sub>-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.\"</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"28-36"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On-Line High-Volume Hemodiafiltration: Mechanisms and Equipment.","authors":"Bernard Canaud, Alfred Gagel","doi":"10.1159/000552996","DOIUrl":"https://doi.org/10.1159/000552996","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Narrative review of physiological principles, transport mechanisms, and technical requirements underpinning HDF, integrated with current clinical evidence and engineering considerations.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"58-76"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed Belmouaz, Etienne Cogne, Estelle Desport, Florent Joly, David Lieurain, Antoine Thierry
{"title":"Vitamin E-Coated Super High-Flux Membranes: Toward Enhanced Middle Molecule Removal and Improved Biocompatibility.","authors":"Mohamed Belmouaz, Etienne Cogne, Estelle Desport, Florent Joly, David Lieurain, Antoine Thierry","doi":"10.1159/000552909","DOIUrl":"https://doi.org/10.1159/000552909","url":null,"abstract":"<p><p>End-stage renal disease is characterized by the accumulation of uremic toxins, chronic inflammation, and heightened oxidative stress, all of which contribute to high morbidity and mortality among hemodialysis (HD) patients. Although conventional HD effectively removes small solutes, inadequate clearance of large middle molecules remains a major therapeutic limitation. The development of medium cut-off and super high-flux (SHF) membranes has enabled enhanced removal of large middle molecules within the framework of Expanded Hemodialysis (HDx). In parallel, strategies aimed at improving membrane biocompatibility, particularly vitamin E-coated membranes, have been developed to mitigate inflammation and oxidative stress production triggered by the interaction between blood and dialysis membranes. This review summarizes the effects of HDx on the removal of middle molecules, and outlines emerging evidence supporting vitamin E-coated SHF membranes as an approach to combine improved middle molecules clearance with enhanced biocompatibility.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"114-123"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Dialyzer Classification in Japan.","authors":"Masanori Abe","doi":"10.1159/000552906","DOIUrl":"https://doi.org/10.1159/000552906","url":null,"abstract":"<p><p>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 β<sub>2</sub>-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.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"37-48"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expanded Hemodialysis: From Operational Mechanism to Clinical Results.","authors":"Claudio Ronco","doi":"10.1159/000552967","DOIUrl":"https://doi.org/10.1159/000552967","url":null,"abstract":"<p><p>Research has produced interesting advances in the area of hemodialysis and related technology. Innovative composition and nanotechnology-related production techniques have produced new membranes with improved biocompatibility and enhanced permeability. Such membranes defined \"medium cut-off\" (MCO) have led to a new dimension of dialysis adequacy. Clearance of medium- and high-molecular-weight solutes (i.e., uremic toxins in the range of 5-30 kDa) is increased, thanks to a specific sieving profile in the region of retention onset (i.e., the molecular weight where the sieving value is 0.9). Retention onset of these membranes shifts to the right in the sieving profile compared to high-flux membranes, while the cut-off remains almost unchanged (i.e., sieving value of 0.1) with marginal albumin leakage. Therefore, MCO membranes have also been defined with the term \"high retention onset.\" The application of MCO/high retention onset membranes with a classic dialysis apparatus characterizes the technique called \"expanded hemodialysis.\" The technique relies on internal filtration and backfiltration mechanism that, combined with sieving characteristics of MCO membranes, produce significant clearance of large middle molecules. This mechanism is maximized if hollow fibers with reduced inner diameter are employed. The minimum technical requirement makes expanded hemodialysis application possible in every setting, where the quality of dialysis fluid meets current standards. This new technique has led to significant results in terms of biochemical targets, biological profiles, and clinical outcomes.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"105-113"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unmet Clinical Needs and New Dialytic Approaches: Expanding the Therapeutic Horizon in Hemodialysis.","authors":"Maria Gabriela Guimarães, Gonzalo Ramírez-Guerrero, Thiago Reis, Mayra Estacio, Claudio Ronco","doi":"10.1159/000552895","DOIUrl":"https://doi.org/10.1159/000552895","url":null,"abstract":"<p><p>Blood purification in patients on maintenance dialysis has evolved far beyond the historical paradigm of urea removal, reflecting a deeper understanding of the biological complexity of uremia. Despite technological advances in conventional hemodialysis (HD), persistent cardiovascular mortality, accelerated loss of residual kidney function, and sustained symptom burden underscore the limitations of diffusion-dominant therapy. Uremic toxins, including middle-to-large molecules and protein-bound toxins, contribute to systemic inflammation, vascular injury, and multiorgan dysfunction, necessitating broader clearance strategies. Hemodiafiltration (HDF), expanded hemodialysis (HDx), and hemoadsorption combined with HD represent a triad of emerging approaches designed to address these unmet clinical needs. High-volume HDF has demonstrated a dose-dependent survival advantage, reinforcing the clinical relevance of convective intensity. HDx offers enhanced middle-molecule clearance within a simplified operational framework, using back-filtration as its core mechanism to achieve broader molecule clearance through medium-cut-off membranes. Adsorptive techniques further expand the therapeutic spectrum by targeting protein-bound and inflammatory solutes using sorbent materials inserted in a cartridge configuration in line with the HD circuit. Differences in clearance profiles across modalities translate into signals for survival, preservation of residual kidney function, and improvements in patient-reported outcomes. Together, these strategies redefine dialysis as a mechanism-driven, individualized intervention aimed at improving patient care.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hemoadsorption/Hemodialysis: Rationale, Indications, and Practical Application.","authors":"Gonzalo Ramírez-Guerrero, Cristian Pedreros-Rosales, Matteo Marcello, Claudio Ronco","doi":"10.1159/000552912","DOIUrl":"https://doi.org/10.1159/000552912","url":null,"abstract":"<p><p>Uremic toxicity extends beyond small solutes to include middle molecules and protein-bound uremic toxins (PBUTs), which are inadequately removed by conventional dialysis. These limitations arise from membrane-dependent transport mechanisms and the high-affinity binding of PBUTs to albumin, restricting their effective clearance. Hemoadsorption, when coupled with hemodialysis (HAHD), provides a complementary approach by enabling direct physicochemical interactions between circulating solutes and sorbent materials, thereby overcoming constraints related to molecular size and protein binding. The concept of residual uremic toxicity highlights the persistence of biologically active solutes despite optimized dialysis delivery. In this context, patient selection should follow a phenotype-based, toxin-domain approach. Four main phenotypes are proposed: inflammatory, PBUT-driven symptom, middle-molecule burden, and neurocognitive. Each phenotype reflects a dominant toxin profile and provides a rationale for targeted extracorporeal strategies beyond conventional adequacy metrics. HAHD should be considered in patients with persistent symptoms, inflammation, or biochemical abnormalities despite optimized therapy. Treatment prescription must be individualized, integrating frequency, duration, and blood flow to reduce cumulative toxin burden over time. Emerging evidence suggests that HAHD may improve inflammatory markers, patient-centered outcomes, and potentially survival. Overall, HAHD represents a phenotype-driven strategy to better align extracorporeal therapies with the complex biology of uremia.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"124-136"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dialysis Membranes and Hemodialyzers.","authors":"William R Clark, Anna Lorenzin, Claudio Ronco","doi":"10.1159/000552907","DOIUrl":"https://doi.org/10.1159/000552907","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10725,"journal":{"name":"Contributions to nephrology","volume":"201 ","pages":"13-27"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}